The proceeds will fund the advancement of the company's first-in-class drug candidate AF-219 for the treatment of pathologic cough, including for cough in IPF patients, as well as advancement of its next candidate compound to the clinic for cardiovascular and other diseases. AF-219 is a selective, non-narcotic and orally administered P2X3 antagonist. The oversubscribed Series C financing was led by Fidelity Management & Research Company, with participation from other crossover funds Jennison Associates LLC (on behalf of certain clients), New Leaf Ventures, Partner Fund Management, Redmile Group, Tekla Healthcare Investors and Tekla Life Science Investors, in addition to an undisclosed blue chip public investment fund.

In other news, the company noted that its multi-center, dose-escalation Phase 2b study of AF-219 in patients with chronic cough has recently completed enrollment. Top-line data from this study is expected in September. Results from an earlier proof-of-concept Phase 2 study in chronic cough patients published in The Lancet demonstrated that AF-219 reduced cough frequency by 84%, as measured objectively with a cough recorder device. Afferent also plans to initiate this year a Phase 2 study of AF-219 for the treatment of chronic cough in IPF patients, an orphan indication affecting approximately 85,000 patients in the U.S.

Kathleen Sereda Glaub, Afferent's chief executive officer, stated, 'This strong Series C round provides additional optionality for Afferent value creation, while funding our dose selection studies and other studies needed to prepare our first-in-class compound, AF-219, for Phase 3 trials in pathologic cough, including in patients with IPF. We also will progress our next compound to the clinic later this year, for cardiovascular and other diseases involving P2X3-driven afferent sensitization, as we continue to validate our P2X3 platform capabilities and further elucidate the role of this important biological mechanism that drives debilitating and chronic disorders.'

'Afferent is an industry leader in the research and development of P2X3 antagonists with clear proof-of-concept clinical data in chronic cough, a smart strategy for clinical development, and most importantly, a highly experienced team,' said Kevin Starr, chairman of the board for the company and partner of Third Rock Ventures. 'We welcome the addition of these top-tier, public investors to the syndicate, which will provide the resources needed to advance treatments that ultimately may benefit millions of patients.'

Pathologic Cough - Debilitating & Potentially Chronic Neurogenic Disorder Affecting Millions

Cough is the symptom for which patients most often seek medical attention. Pathologic cough or non-productive cough serves no functional purpose, and can occur following an upper respiratory infection. In most patients, this cough manifests itself as an acute cough lasting a few weeks. However, in some patients, sensitized nerve fibers fail to return to a normal quiescent state, resulting in sub-acute or chronic cough lasting months to years. The prevalence of chronic cough is estimated to be over 10% of adults in the U.S. While an underlying etiology may contribute to cough in some of these patients (such as GERD, asthma, COPD, etc.), 20-40% of these are not responsive to treatment for such underlying etiology or have no known trigger. Additionally, many treatment-responsive patients are not well-controlled for their cough.

Pathologic cough, particularly if chronic, can become life-altering for patients, affecting overall quality of life, and ability to maintain relationships or jobs. Social isolation and depression often become significant factors for these patients, as pathologic coughers are ostracized in public venues such as the workplace, restaurants, public transport, theaters, etc. Many chronic cough patients cough persistently especially during the active daytime period. Patients with IPF are among those with the most severe cough, the most debilitating symptom of their disease. In Afferent's proof-of-concept Phase 2 study, chronic cough patients enrolled were, on average, coughing approximately 40 times per hour for over 10 years before treatment.

Currently available antitussive drugs have shown little objective evidence that they are effective for cough in any disorder. Further, safety and abuse liability concerns have restricted use of certain narcotic antitussives. The last new cough therapy to be approved was dextromethorphan nearly 50 years ago. To date, no other agent in development has shown effectiveness in the treatment of pathologic cough, especially using objective measures of cough frequency.

P2X3 Receptors Role in Hyper-sensitization and Pathology

The P2X3 receptor, the target for Afferent's lead AF-219, is predominantly expressed in C-fiber primary afferent nerves that innervate most tissues and organs, including the skin, joints, and the hollow organs such as the airways and bladder. These primary afferent neurons are not important in normal physiological or defensive sensing processes, but rather become activated and sensitized under pathological conditions by a common cellular signal ATP, such as following nerve injury, infection or inflammation.

P2X3 receptor-mediated sensitization has been implicated in inflammatory, visceral and neuropathic pain states, as well as airways hyper-reactivity, migraine, itch and cancer pain.

Afferent's first-in-class compounds selectively target P2X3 channels in order to block the activation of these afferents by ATP.

About Afferent Pharmaceuticals

Afferent Pharmaceuticals is a clinical-stage biotechnology company and leader in the development of novel drugs for the treatment of a range of debilitating neurogenic disorders. These disorders affect millions of patients who suffer from chronic respiratory and urologic sensory pathologies as well as chronic pain, and who have limited, if any, treatment options. These chronic pathologies arise when certain nerve fibers become hyper-sensitized as a result of inflammation, distress, infection or tissue injury, and sometimes remain chronically sensitized for months and even years.

Afferent is developing molecules that selectively block P2X3, a purinergic receptor, which plays a key role in the sensitization of these nerves. Afferent's lead molecule, AF-219, is a first-in-class P2X3 antagonist, and is being developed for the treatment of pathologic cough. Data from a Phase 2 proof-of-concept study is the foundation for a full development program currently under way to further evaluate treatment of any pathologic cough as well as cough in idiopathic pulmonary fibrosis (IPF) patients.

An industry-leading position and platform capabilities in the research and development of P2X3 antagonists enables Afferent to widely explore this important mechanism of action and evaluate its utility in a broad range of indications. These indications include respiratory disease (pathologic cough, including acute, sub-acute and chronic cough, IPF cough, asthma, COPD), visceral sensory disorders such as chronic pelvic pain syndrome (interstitial cystitis/bladder pain syndrome) and chronic prostatitis (overactive bladder), resistant hypertension, chronic pain in the joints, and various other chronic pain disorders, including migraine.