FDA approves Proteostasis’s triple combination program for CF

Singapore — Proteostasis Therapeutics, a clinical stage biopharmaceutical company dedicated to the discovery and development of ground-breaking therapies to treat cystic fibrosis (CF) and other diseases caused by dysfunctional protein processing, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for the Company’s triple combination program for the treatment of cystic fibrosis. The Company’s proprietary triple combination includes a novel cystic fibrosis transmembrane conductance regulator (CFTR) amplifier, third generation corrector and potentiator, known as PTI-428, PTI-801 and PTI-808, respectively. The Company announced in January that the protocol for its triple combination clinical study, which the Company plans to initiate in the current quarter, has received endorsement and a high strategic fit score from the Therapeutics Development Network (TDN) and the Clinical Trial Network (CTN), the drug development arms of the Cystic Fibrosis Foundation (CFF) and the European CF Society (ECFS), respectively.

“Fast Track designation represents another positive step for the development of our triple combination therapy and underscores the serious unmet need that remains for the vast majority of CF patients,” said Meenu Chhabra, president and chief executive officer of Proteostasis Therapeutics.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track program designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design and may be eligible for priority review if certain criteria are met.

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Low Level of Zinc Ions in Lungs Contribute to Buildup of Mucus in CF

When two channels that are supposed to move chloride and sodium ions out of cells in the lungs fail to function properly, it leads to the mucus buildup seen in cystic fibrosis.

Japanese researchers have discovered that the channel dysfunctions also reduce the amount of zinc ions going into the lungs, further contributing to the thick mucus accumulation.

Their study, published in the journal EBioMedicine, is titled “Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells.Continue reading Low Level of Zinc Ions in Lungs Contribute to Buildup of Mucus in CF

Cancer gene plays key role in cystic fibrosis lung infections

PTEN is best known as a tumor suppressor, a type of protein that protects cells from growing uncontrollably and becoming cancerous. But according to a new study from Columbia University Medical Center (CUMC), PTEN has a second, previously unknown talent: working with another protein, CFTR, it also keeps lung tissue free and clear of potentially dangerous infections.

The findings, published in Immunity, explain why people with cystic  are particularly prone to respiratory infections—and suggest a new approach to treatment.

A quarter-century ago, researchers discovered that cystic fibrosis is caused by mutations in the CFTR gene, which makes an eponymous protein that transports chloride ions in and out of the cell. Without ion transport, mucus in the lung becomes thicker and stickier and traps bacteria—especially Pseudomonas—in the lung. The trapped bacteria exacerbate the body’s inflammatory response, leading to persistent, debilitating infections.

But newer research suggests CFTR mutations also encourage infections through a completely different manner.

“Recent findings suggested that  with CFTR mutations have a weaker response to bacteria, reducing their ability to clear infections and augmenting inflammation,” said lead author Sebastián A. Riquelme, PhD, a postdoctoral fellow at CUMC. “This was interesting because it pointed to a parallel deregulated immune mechanism that contributes to airway destruction, beyond CFTR’s effect on mucus.”

That’s where PTEN comes into play. “We had no idea that PTEN was involved in cystic fibrosis,” said study leader Alice Prince, MD, professor of pediatrics (in pharmacology). “We were studying mice that lack a form of PTEN and noticed that they had a severe inflammatory response to Pseudomonas and diminished clearance that looked a lot like what we see in patients with cystic fibrosis.”

Delving deeper, the CUMC team discovered that when PTEN is located on the surface of lung and immune cells, it helps clear Pseudomonas bacteria and keeps the inflammatory response in check. But PTEN can do this only when it’s attached to CFTR.

And in most cases of cystic fibrosis, little CFTR finds it way to the cell surface. As a result, the duo fail to connect, and Pseudomonas run wild.

As it happens, the latest generation of cystic fibrosis drugs push mutated CFTR to the cell surface, with the aim of improving chloride channel function and reducing a buildup of mucus. The new findings suggest that it might be beneficial to coax nonfunctional CFTR to the surface as well, since even abnormal CFTR can work with PTEN to fight infections, according to the researchers.

“Another idea is to find drugs that improve PTEN membrane anti-inflammatory activity directly,” said Dr. Riquelme. “There are several PTEN promotors under investigation as cancer treatments that might prove useful in cystic fibrosis.”

The study also raises the possibility that PTEN might have something to do with the increased risk of gastrointestinal cancer in . “With better clinical care, these patients are living much longer, and we’re seeing a rise in gastrointestinal cancers,” said Dr. Prince. “Some studies suggest that CFTR may be a tumor suppressor. Our work offers an alternative hypothesis, where CFTR mutations and lack of its partner, PTEN, might be driving this cancer in patients with .”

The paper is titled, “Cystic fibrosis transmembrane conductance regulator attaches tumor suppressor PTEN to the membrane and promotes anti Pseudomonas aeruginosa immunity.”

For journal article click here:

http://www.cell.com/immunity/fulltext/S1074-7613(17)30487-9

Positive Results for Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced that the New England Journal of Medicine (NEJM) published two articles with results from two Phase 3 studies of the tezacaftor/ivacaftor combination treatment, a medicine in development that is designed to treat the underlying cause of cystic fibrosis (CF) in people ages 12 and older who have certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Continue reading Positive Results for Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment

Live Stream the North American CF Conference Tomorrow for Free!

The North American CF Conference (NACFC) provides a collaborative and educational forum for all CF professionals. The educational elements of the meeting program are targeted to physicians, nurses, research scientists, respiratory therapists, physical therapists, nutritionists, social workers, and pharmacists. Continue reading Live Stream the North American CF Conference Tomorrow for Free!

Phase 1a study for drug to treat CF regardless of CF Mutation

http://www.businesswire.com/news/home/20171018005403/en/Synspira-Announces-Patient-Dosed-Phase-1a-Study

Synspira Announces First Patient Dosed in Phase 1a Study of SNSP113 in Cystic Fibrosis
— First-in-class drug candidate for treatment of cystic fibrosis regardless of genetic mutation — Continue reading Phase 1a study for drug to treat CF regardless of CF Mutation

Lab-made “mini organs” helping doctors treat cystic fibrosis

http://www.seattletimes.com/nation-world/lab-made-mini-organs-helping-doctors-treat-cystic-fibrosis/

Els van der Heijden, who has cystic fibrosis, was finding it ever harder to breathe as her lungs filled with thick, sticky mucus. Despite taking more than a dozen pills and inhalers a day, the 53-year-old had to stop Continue reading Lab-made “mini organs” helping doctors treat cystic fibrosis

New cystic fibrosis biotech aims to take a different approach than Vertex

http://www.bizjournals.com/

California-based Synedgen has spun out its experimental cystic fibrosis treatments into a new biotech to be based in the Boston area, with an eye toward complementing existing drugs for the lung disease. Continue reading New cystic fibrosis biotech aims to take a different approach than Vertex

Phase 1 Data for SPX-101 at the European Cystic Fibrosis Conference

Spyryx Biosciences Expands Development Award with Cystic Fibrosis Foundation; Presents Phase 1 Data for SPX-101 at the European Cystic Fibrosis Conference
-No dose-limiting adverse effects in 14-day multiple ascending dose study
-The Company to receive up to total of $5 million to support Phase 2 trial

DURHAM, N.C., June 20, 2017 – Spyryx Biosciences, Inc., a clinical stage biopharmaceutical company developing innovative therapeutics to address Continue reading Phase 1 Data for SPX-101 at the European Cystic Fibrosis Conference

Clinical and Regulatory Progress Across Pipeline Programs for Drug Company

http://www.nasdaq.com/press-release/proteostasis-therapeutics-announces-clinical-and-regulatory-progress-across-pipeline-programs-20170607-00270

Proteostasis Therapeutics Announces Clinical and Regulatory Progress Across Pipeline Programs

Updates Announced During the 40th European Cystic Fibrosis Society Conference

Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a biopharmaceutical company developing small molecule therapeutics to treat diseases caused by Continue reading Clinical and Regulatory Progress Across Pipeline Programs for Drug Company