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  • Patients with Mild Cognitive Impairment treated with CHF 5074 for up to 90 weeks demonstrated highly statistically significant improvements in verbal memory and executive function
  • CHF 5074 is a first-in-class small molecule microglia modulator, the only compound of its kind in clinical development for the treatment of MCI and for prevention of Alzheimer’s disease
  • Data were presented at the Alzheimer’s Association International Conference 2013 (AAIC 2013)
  • AAIC 2013 highlighted CHF 5074 as one of four recent research trials investigating new targets for therapies in Alzheimer’s disease and incorporating novel approaches to participant identification and selection
  • CereSpir and Chiesi are negotiating a License Agreement, which will grant CHF 5074 global development and commercialization rights to CereSpir

July 26, 2013 – New York, NY – CereSpir™ Incorporated announced positive interim clinical results from Chiesi Farmaceutici’s Phase 2 study testing CHF 5074, a novel, first-in-class small molecule microglia modulator, in patients with mild cognitive impairment (MCI).  The 90-week study, which included a 96-patient 14-week double-blind, placebo-controlled study and an ongoing 76-week open-label extension study, tested three titrated doses of CHF 5074 (200 mg, 400 mg, 600 mg dosed orally once daily) in MCI patients.  Upon completion of the 14-week study, 74 MCI patients enrolled in the open-label extension study and continued receiving CHF5074 at the dose equal to that of their originally assigned double-blind study cohort.  Interim analysis of cognitive tests of 30 patients reaching Study Week 88 showed statistically significant improvements compared to baseline on

  • Digit Symbol Substitution Test (+4.3 ± 1.4 matches p < 0.003)
  • Trail Making Test-A (-7.0 ± 2.4 sec, p = 0.007)
  • Trail Making Test-B (-7.4 ± 6.8 sec, p = 0.291)
  • Immediate Word Recall (+3.7 ± 0.9 words, p < 0.001)
  • Delayed Word Recall (+1.2 ± 0.4 words, p = 0.012)
  • Composite Hopkins Verbal Learning Score (5.0 ± 1.4 (0.001)

Interestingly, ApoE4 carriers (n=12) performed significantly better (p<0.05) than ApoE4 non-carriers on Immediate Word Recall and Trail Making Test-A with improvements representing 25-38% of baseline scores.

“This is one of the first studies to show a neuroinflammatory inhibitor may be able to improve cognition in people with MCI.  CHF 5074 has the potential to treat patients at the earliest stages of the disease, as well as prevent onset of the disease in healthy individuals who are at risk of developing Alzheimer’s,” stated Joel Ross, MD, FACP, AGSF, CMD, CPI, of the Memory Enhancement Center of American in Eatontown, NJ, who was the principle investigator of the study and who presented the results at AAIC 2013.  “I personally am very excited CereSpir was created exclusively to move this important small molecule into Phase 3 development.”

CereSpir™ Incorporated and Chiesi Farmaceutici S.p.A. today acknowledged the Companies have entered into a Letter of Intent and are negotiating a Licensing Agreement, whereby CereSpir will acquire the exclusive global development and commercialization rights to CHF 5074.

In the double-blind, placebo-controlled phase of the study, treatment with CHF 5074 resulted in a dose-depended reduction in inflammatory biomarkers (TNF-alpha and sCD40L) in cerebrospinal fluid collected after 12 weeks of dosing.

“We are encouraged by the sustained cognitive improvement observed in MCI patients after prolonged treatment with CHF 5074, especially the response seen in ApoE4 carriers,” stated Daniel Chain, PhD, CereSpir’s President and CEO.  “These results substantiate the large body of data from published preclinical studies, which indicates the compound reduces neuroinflammation, inhibits brain Aβ plaque deposition, reduces tau pathology, and reverses associated memory deficits in AD transgenic mouse models thus acting simultaneously on several important therapeutic targets.”

Seventy-four patients entered the open-label study: 26 continued on 200 mg/day, 21 continued on 400 mg/day, and 27 continued on 600 mg/day.  Patients were monitored for vital signs, cardiac activity, neuropsychological performance and safety laboratory parameters.  At Study Week 40, 14 patients dropped out: four, two, and eight in the 200, 400, and 600 mg/day cohorts, respectively.  Three of drop-outs were for adverse events: two in the 600 mg/day group (serum creatinine elevation and worsening of cognitive function), and one in the 400 mg/day group (pneumonia).  The most frequent treatment-emergent adverse events were gastrointestinal disorders, with diarrhea being reported by 1.4% of patients on 200 mg/day, 6.3% of patients on 400 mg/day, and 20.0% of patients on 600 mg/day.

About CHF 5074
CHF 5074 is a small molecule with a unique microglial modulating mechanism of action capable of selectively reducing pro-inflammatory activities of microglial cells while increasing their ability to remove neurotoxic amyloid beta (“Aβ”) aggregates in the brain by phagocytosis.  Microglia are small cells that migrate through the brain to remove waste products, such as amyloid aggregates that cause inflammation and irreversible damage to nerve cells.  Chronic dysfunction of microglia is increasingly believed to play an important role at the very beginnings of Alzheimer’s disease.  The results from Chiesi’s human clinical studies corroborate the large body of data from published preclinical studies.  In Alzheimer’s disease transgenic mouse models, CHF 5074 was shown to reduce neuroinflammation, inhibit brain amyloid β plaque deposits, reduce tau pathology, and reverse associated memory deficits.  These findings indicate CHF 5074 acts simultaneously on several important therapeutic targets, and this multi-target approach may translate into preventing the memory loss that is the hallmark of Alzheimer’s disease.

AAIC 2013 highlighted CHF 5074 as one of four recent research trials investigating new targets for therapies in Alzheimer’s disease and incorporating novel approaches to participant identification and selection.

About Alzheimer’s disease, ApoE4, and Mild Cognitive Impairment
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and the leading cause of dementia among the elderly.  More than 30 million people are afflicted with AD, with the associated estimated cost of care exceeding $200 billion annually, as patients live eight to ten years on average after diagnosis.  Today, AD remains the largest unmet medical need in neurology, with the disease expected to afflict 100 million by 2050.

Individuals who have the ApoE 4 gene are three to eight times more likely to develop AD than those who do not carry ApoE 4.  The level of risk partially depends on whether the person inherits one or two copies of the gene.  ApoE4 causes a more aggressive form of AD that is believed to involve a strong inflammatory response.

Mild Cognitive Impairment (MCI) causes cognitive changes that are serious enough to be noticed by the individuals experiencing them or to other people, but the changes are not severe enough to interfere with daily life or independent function; therefore, they do not meet diagnostic guidelines for dementia.  However, those with MCI, particularly ApoE4 carriers, have an increased risk of eventually developing Alzheimer’s or another type of dementia.

About Chiesi Farmaceutici S.p.A.
Founded in 1935 in Parma (Italy), the Chiesi Group achieved in 2012 a turnover of € 1,107 million, an increase of 4.7% in comparison with the previous year. The Group, whose main areas of activity are in respiratory therapies and specialist medicine, currently has 25 branches worldwide and is present in over 60 countries with its products, produced at the plants in Parma, Blois (France) and Santana de Parnaíba (Brazil).

In 2012 investment in R&D reached € 198 million, accounting for 18% of sales, a level that the company intends to maintain in coming years. The R&D operations in Parma, Paris, Rockville (USA) and Chippenham (UK) integrate their efforts to advance the Group’s pre-clinical, clinical and registration programs. At the end of 2012, the Chiesi Group employed over 3,800 people and more than 350 of them were involved in R&D.

About CereSpir Incorporated
CereSpir is dedicated to preserving the primary essence of each person, his or her memories.  The privately held company was founded by Daniel Chain, PhD, to focus exclusively on the final development of CHF 5074, upon the completion of a licensing agreement with Chiesi Farmaceutici S.p.A.  Dr. Chain is a seasoned, accomplished and knowledgeable entrepreneur, inventor and CEO who has spearheaded the development of several innovative therapeutic approaches in his unrelenting pursuit of a world without Alzheimer’s disease.