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Afferent Clinical Data for Lead Candidate, AF-219, Demonstrate Improvements in Pain and Urinary Urgency in Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS)Afferent Pharmaceuticals, a leader in the development of small molecule compounds targeting P2X3 for the treatment of respiratory and urologic disorders, as well as chronic pain, today announced presentation of results from a Phase 2 clinical trial demonstrating that the company's first-in-class drug candidate, AF-219, improved symptoms of pain and urinary urgency in patients with moderate to severe symptoms of interstitial cystitis /bladder pain syndrome (IC/BPS). AF-219 is a selective, non-narcotic and orally administered P2X3 antagonist that targets the mechanism by which certain nerve fibers become hyper-sensitized and can lead to chronic and debilitating symptoms in diverse conditions. Previous findings published in The Lancet showed that AF-219 reduced daytime cough frequency by 75% compared to placebo in patients with treatment-refractory chronic cough. The current clinical data in IC/BPS are being featured this week in two oral presentations during the SUFU 2015 Winter Meeting, taking place in Scottsdale, Arizona, February 24-28. In the 74-patient titration portion of this randomized, double-blind, placebo-controlled Phase 2 clinical trial, patients were randomly assigned to either AF-219 or placebo treatment twice daily for four weeks, with AF-219 titrated from 50 mg to 300 mg in the first week and provided on a fixed-dose basis in weeks 2-4. Post-week 4, all patients were followed up for an additional two weeks. Data from the study demonstrated a positive trend in the improvement of Numeric Pain Rating Scale (NPRS) pain score in AF-219-treated patients compared to placebo, and AF-219-treated patients showed a significant reduction in urinary urgency, the cardinal symptom of IC/BPS, compared to placebo. Safety and tolerability findings were similar between AF-219-treated patients and those receiving placebo, except that higher numbers of the AF-219-treated patients experienced temporary changes in their sense of taste. "Patients with IC/BPS often suffer debilitating symptoms that can interfere with daily commitments and social interactions," commented Philp Hanno, M.D., lead clinical investigator in the IC/BPS study, and Professor of Urology in Surgery at the Hospital of the University of Pennsylvania. "Unfortunately, this condition is often under-treated due to the lack of therapeutic options, and new approaches are greatly needed." Dr. Hanno continued, "Symptoms can be very difficult to treat in this patient population, and I am excited to be able to report clear clinical benefit and encouraging results in both pain and urinary urgency in this phase 2 IC/BPS trial. I look forward to further studies being planned in the future." Anthony Ford, Ph.D., Founder and Chief Scientific Officer of Afferent Pharmaceuticals, stated, "A key advantage of our approach is that the target P2X3 receptors have limited distribution beyond sensory nerves and no significant expression in the higher centers of the brain. AF-219 offers an alternative approach that we believe can limit the serious CNS side effects associated with many pain and urological treatments." Kathleen Sereda Glaub, Afferent's chief executive officer, stated, "Afferent has built a broad knowledge base and substantial proof of concept for AF-219, having completed nine clinical trials of this promising drug candidate. Based on results published late last year in The Lancet, we intend to initiate several clinical trials, including Phase 2b testing in patients with chronic cough as well as in patients with idiopathic pulmonary fibrosis associated cough and breathlessness this year. We are proud of the work of our investigator network and internal research teams, and we look forward to continued progress of our clinical program." About IC/BPS IC/BPS is an idiopathic syndrome in which patients experience chronic pain, pressure or discomfort, perceived to be related to the urinary bladder. Patients also experience the urge to urinate and/or urinary frequently. IC/BPS may be more common than previously thought, affecting mostly women. Symptoms of IC/BPS may be experienced by 2.7-6.5% of women. Current treatments for IC/BPS have limited efficacy. A large body of data published over the last decade have indicated that P2X3 antagonism may be an ideal approach to suppress inappropriate sensory signaling in lower urinary tract tissues that underlies the highly bothersome symptoms of IC/BPS: from preclinical gene-deletion models, pharmacological studies, and assessments of pathological changes in patient samples. Afferent's Phase 2 study is the first P2X3 inhibitor to be studied in clinical trials in IC/BPS. P2X3 Receptors Role in Hyper-sensitization and Pathology P2X3 receptors are novel targets, highly specific to unmyelinated, small diameter C fiber afferent (or sensory) nerves that have dense innervations in visceral organs, skin and joints and which transmit pain and other sensations of organ function. In contrast, P2X3 receptors are absent in higher brain centers. ATP (News - Alert), released by stressed, inflamed or injured tissues, has been found to be the sole ligand for P2X3 receptors, and overstimulation with ATP can cause hyper-sensitization and overactivity of the C fiber afferent nerves, which in turn can lead to diverse manifestations and symptoms in common diseases, many of which are poorly met medically. Afferent's substantial preclinical and clinical data validate P2X3 as an important target for the treatment of respiratory and urologic disorders, as well as chronic pain. About Afferent Pharmaceuticals Afferent Pharmaceuticals is a clinical-stage biotechnology company and leader in the development of first-in-class, small molecule compounds that target P2X3 receptors for the treatment of respiratory and urologic disorders, as well as chronic pain. Afferent's industry-leading position in the research and development of P2X3 antagonists enables the company to widely explore this novel mechanism of action and evaluate its utility in a broad range of indications. These indications include respiratory disease (acute, sub acute and chronic cough, IPF, asthma, COPD), pelvic pain and hyperactivity (interstitial cystitis/bladder pain syndrome (IC/BPS), overactive bladder), resistant hypertension, chronic pain in the joints, and various other chronic pain disorders, including migraine. Afferent's platform is built on more than a decade of research on P2X3 receptors and P2X3 antagonists. The company's lead candidate, AF-219, is expected to be evaluated in a Phase 2b study initiating in 1Q 2015. A second and differentiated P2X3 antagonist will be evaluated in IND-enabling studies in 1Q 2015. Additionally, the company's pipeline of P2X3 antagonists represents diverse and further differentiated molecules that are being evaluated for multiple indications. For more information on the company, please visit Afferent's website at www.afferentpharma.com.
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