PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today that its joint development program in Spinal Muscular Atrophy (SMA) with Roche and the SMA Foundation (SMAF) has started a Phase 1b/2a study in adult and pediatric patients. The placebo-controlled, randomized, multiple-dose study will enroll approximately 48 patients with SMA and investigate the safety and tolerability of an investigational survival of motor neuron 2 (SMN2) gene splicing modifier (RG7800) over 12 weeks. The achievement of this milestone triggers a $10 million payment to PTC from Roche.

"We are excited to initiate the next phase of this program and begin a trial in SMA patients with our partners," stated Stuart Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics. "We believe that the encouraging clinical results and preclinical data from relevant disease models are promising indications that the orally administered small molecule RG7800 has the potential to modify the splicing of the SMN2 gene and generate more full-length SMN mRNA in SMA patients. The advancement of this potential new treatment, which could represent the first orally available SMN2 splicing modifier for SMA, is a significant milestone for patients and their families."

As previously reported, the Phase 1 single-ascending dose study in healthy volunteers demonstrated that all doses studied were safe, well tolerated and demonstrated a dose-dependent effect on SMN2 splicing as shown by a change in the ratio of full-length SMN2 mRNA to SMN2 mRNA without exon 7 (SMND7), which is interpreted as proof of mechanism in terms of the expected pharmacodynamic effect.

SMA is caused by a missing or defective SMN1 gene, which results in reduced levels of SMN protein. This genetic neuromuscular disease is responsible for the loss of motor neurons within the spinal cord leading to muscle atrophy and death at infant age in its most severe form. We believe the oral small molecule RG7800 may have the potential to target the underlying cause of the disorder by increasing SMN protein levels in the nervous system, muscles, and other tissues. It is estimated that one in 10,000 children in the United States are born with this rare disorder.

The SMA program was initially developed by PTC Therapeutics in partnership with the SMA Foundation. The SMA Foundation was established in 2003 to accelerate the development of a treatment for SMA. In November 2011, Roche gained an exclusive worldwide license to the PTC/ SMAF SMA program. The development of RG7800 is being led by Roche and overseen by a joint steering committee with members from Roche, PTC and the SMA Foundation.

Omeros Corporation (NASDAQ: OMER) announced positive data using OMS721, the lead human monoclonal antibody for its mannan-binding lectin-associated serine protease-2 (MASP-2) program, to inhibit thrombus formation in an ex vivo pathophysiologic system of human atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy (TMA). TMAs are a family of rare, debilitating and life-threatening disorders characterized by excessive thrombi (clots) in the microcirculation of the body's organs, most commonly the kidney and brain. OMS721 is currently in a Phase 2 clinical program evaluating the drug's efficacy in treating TMAs, including aHUS.

The data announced today resulted from studies in a well-established experimental model of TMA aimed at assessing the potential therapeutic benefits of OMS721 in TMA using serum samples from aHUS patients with different etiologies obtained during the acute phase of disease as well as during remission. The studies were conducted by Prof. Giuseppe Remuzzi and colleagues Marina Noris and Miriam Galbusera at the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and the Clinical Research Center for Rare Diseases "Aldo e Cele Dacco" of the same institute, a European center for the study of TMA. The experimental model is based on the finding that sera from aHUS patients promote the formation of thrombi on human microvascular endothelial cells, the defining pathological feature of TMA.

The studies reported today showed that OMS721 significantly inhibited thrombus formation when added to serum samples from aHUS patients obtained during the acute phase of disease (p<0.01) as well as during remission (p<0.0001). OMS721 was as effective at inhibiting thrombus formation as the positive control in the studies – soluble complement receptor 1, an agent that completely blocks the complement system.

Earlier this year, Omeros reported that OMS721 also significantly inhibited complement deposition compared to control treatment in an experimental ex vivo pathophysiologic system of complement activation in TMA, again using serum samples from aHUS patients obtained during the acute phase of disease (p<0.01) and during remission (p<0.001). Prof. Remuzzi's laboratories have previously shown in the same complement-activation model that eculizumab (Soliris®), a monoclonal antibody blocking the complement factor C5 that is approved by the FDA and the European Medicines Agency to treat patients with aHUS, also inhibited complement deposition. Data recently published indicate that the ex vivo pathophysiologic system established by Prof. Remuzzi and his colleagues may be useful in assessing the clinical effectiveness of anti-complement therapy in aHUS (Noris et al., Blood (2014) 124:1715).

"We believe that the notable anti-complement and anti-thrombotic activities of OMS721 in serum samples from aHUS patients bode well for the therapeutic potential of OMS721 in thrombotic microangiopathies," stated Prof. Remuzzi, MD, FRCP, Research Coordinator at the Mario Negri Institute and international expert in the study of kidney disease who has contributed major advances to the understanding of the pathophysiology of hemolytic uremic syndrome.

Having demonstrated that the lectin pathway, and MASP-2 specifically, are involved in the pathophysiology of aHUS, Prof. Remuzzi and his team are currently conducting additional experiments to understand the mechanism by which OMS721 blocks ex vivo thrombus formation in aHUS and its effect on endothelial cells, platelets and the alternative pathway of complement.

"Thrombus formation is the central pathological feature of aHUS and other TMAs, so we are particularly pleased with the robust anti-thrombotic activity in serum samples from aHUS patients," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "We believe that these most recent data from Prof. Remuzzi's laboratories meaningfully de-risk our '721 Phase 2 program in TMAs, including aHUS, and we look forward to reporting preliminary efficacy and safety data from the ongoing clinical trial."