May 1, 2017 (Vol. 37, No. 9)

Industry Watch: Acorda’s Road to Appeal Is Likely an Uphill Climb

Acorda Therapeutics has shed 20% of its workforce, and its stock lost more than one-third of its value in the week since a federal court invalidated four of five patents through which the company has protected its top-selling drug, the MS treatment Ampyra® (dalfampridine).

Acorda will seek to overturn the March 31 decision by Judge Leonard Stark of the U.S. District Court for the District of Delaware, which invalidated U.S. Patent Nos. 8,663,685, 8,007,826, 8,440,703, and 8,354,437: “Defendants have proven clearly and convincingly that the Acorda Patents are invalid due to obviousness.”

The company responded by eliminating about 20% of its workforce—some 120 jobs. Acorda shares fell 21% on March 31, to $21.00. Shares fell another 19% by April 6, closing at $17.05.

Stuart E. Pollack, Ph.D., a partner with law firm DLA Piper, told GEN a finding of obviousness can be harder to successfully appeal than findings of anticipation of prior art or claim construction. The invalidated ‘826 patent describes Ampyra as a “therapeutically effective” concentration of 4-aminopyridine (AP). The court found that a hypothetical person of ordinary skill in the art “would have had a reasonable expectation that 4-AP would be ‘therapeutically effective’ in treating MS.”

“Therapeutically effective” also appears in the upheld patent, No. 5,540,938, covering the formulation of Ampyra Extended Release Tablets, 10 mg. That patent expires in 2018, compared with 2025 to 2027 for the invalidated patents.

Unless Acorda wins on appeal, it will face generic competition nine years sooner than it planned. Ampyra accounted for 95% of the company’s total 2016 revenues—$493.358 million of $519.601 million.

Ten companies seek to market generic versions of Ampyra. Acorda settled with seven, but was challenged by the other three—Mylan, Roxane Laboratories, and Teva Pharmaceutical Industries.

Three weeks before the court decision, the four patents were upheld by the Patent Trial and Appeal Board following a challenge from the Coalition for Affordable Drugs.

“Acorda needed to win both the inter partes review challenge and at the district court level to protect their Ampyra franchise,” Paul Matteis and Jeffrey Lin, Ph.D., of Leerink wrote March 31 in a note to investors. 

Discovery & Development: From Peptide Therapeutic Dreams to Reality

Peptides may represent a “just right” solution in drug discovery and development, situated as they are between small molecules and biologics. In general, peptides contain fewer than 50 amino acids and have molecular weights of less than 10 KDa. Although peptides are, in general, rapidly degraded in the human body, surprisingly stable candidate peptides are being identified in combinatorial screens.

Such candidates may be synthesized, without undue effort, given the modularity of peptides and improvements in peptide-synthesizing technology, which includes the incorporation of unnatural amino acids and introduction of alterations analogous to post-translational modifications. Other advances favoring peptides include improvements in drug delivery, such as technologies that enhance oral bioavailability.

These encouraging developments are reflected in recent market projections. According to Future Market Insights, the global peptide therapeutics market is expected to have an annual growth rate of 10% between 2015 and 2025. Similar growth rates have been estimated by Transparency Market Research, which projects that peptide drug market will be valued at $25.4 billion by 2018.

A subset of peptide drugs consists of macrocycles and constrained peptides, which are generally defined as cyclic small molecules or peptides of 500–2,000 Da. Among the companies specializing in such peptides is PeptiDream, a Tokyo-based biopharmaceutical company. It recently announced that it is collaborating with Janssen Pharmaceuticals to discover and optimize peptides for multiple therapeutic targets.

As per its agreement with Janssen, PeptiDream will use its Peptide Discovery Platform System (PDPS) to identify macrocyclic/constrained peptides against multiple metabolic and cardiovascular targets of interest selected by Janssen, and to optimize hit peptides into therapeutic peptides or small molecule products. Janssen also holds an exercisable option for peptide-drug conjugate (PDC) use and applications. Janssen will have the right to develop and commercialize all compounds resulting from the collaboration.

“Over the past few years, PeptiDream has greatly expanded our ability to turn PDPS-identified peptide candidates into peptide therapeutics, small molecule drugs, and peptide-drug conjugates (PDCs),” said Kiichi Kubota, PeptiDream’s CEO and president. “We greatly look forward to working with Janssen to leverage these capabilities to discover and develop the next generation of first-in-class and best-in-class therapeutics.”

Genomics & Proteomics: Strategic Partnership Sets Up Technology Innovation for Genetic Diseases

In the fight against genetically driven-diseases such as Alzheimer’s, Parkinson’s, and cancer, a new strategic partnership between Seven Bridges and Spatial Transcriptomics aims to advance the development of innovative tools for visualizing and analyzing gene expression within tissue samples.

As a first step in building a strategic partnership, Seven Bridges’ investment is aimed at advancing the development of Spatial Transcriptomics’ rich set of gene-expression tools and making those tools available on the Seven Bridges Platform for biomedical analysis, which is used by thousands of researchers working on large-scale genomics projects worldwide.

“Spatial Transcriptomics’ technology enables scientists to ask questions about gene-expression dynamics that were never before possible, with broad applications for large research projects like the Human Cell Atlas, as well as for teams working to develop treatments for genetically driven diseases like diabetes, Alzheimer’s and cancer,” said Brandi Davis-Dusenbery, Ph.D., CEO of Seven Bridges. “Our relationship with Spatial Transcriptomics will help their technology reach more scientists via the Seven Bridges Platform, which aligns with our goal to make leading-edge bioinformatics tools more accessible and useful to researchers around the globe.” 

Spatial Transcriptomics’ innovative approach allows detailed mapping of gene activity within thin sections of various tissues, from humans, animals, and plants. Using this approach, researchers are able to investigate gene-expression dynamics, and the implications of those dynamics on human health, more quickly and at a fraction of the cost of other methods like single-cell sequencing.

“The Seven Bridges Platform makes it much easier for researchers to access, analyze, and share massive biomedical data sets, providing an ideal collaborative environment for all types of genomic research projects,” said Florian Baumgartner, CEO of Spatial Transcriptomics.

By making this technology available on its platform later this year, Seven Bridges will give users the ability to analyze their own gene expression data in conjunction with other large data sets, including The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia.

Bioprocessing: BiondVax Wins Financing for Flu Vaccine Facility

BiondVax Pharmaceuticals, a clinical-phase biopharmaceutical company developing a universal flu vaccine, reports that the Israel Investment Center, a unit of Israel’s Ministry of Economy and Industry, approved a grant representing 20% of its NIS 20 million budget (approximately $5.5 million).

The money will be used toward the construction of a factory for the production of Phase III and commercial batches of BiondVax’s universal flu vaccine candidate M-001. The grant is subject to certain terms and conditions, including those outlined under the Encouragement of Capital Investment Law 1959.

BiondVax plans to build the mid-sized factory in Jerusalem, with potential capacity to annually produce up to tens of millions of doses of M-001. M-001 is designed to provide protection against current and future seasonal and pandemic flu strains.

Five completed Phase I/II and Phase II human clinical trials have shown the vaccine to be safe and immunogenic to multiple flu strains.

“This significant milestone signifies the evolution of BiondVax from a biotech start-up to a pharmaceutical company positioned for significant growth and contributions to society. I would like to thank the Ministry of Economy and Industry for helping translate BiondVax’s vision to reality,” said Ron Babecoff, the company’s CEO.

“In the past few years, BiondVax focused on establishing a small-scale GMP facility, one that was approved by the European Union. Our current facility laid the foundation for manufacturing quality excellence that will be implemented in the new factory,” added Simon Hassin, Ph.D., BiondVax’s COO.

An ongoing Phase IIb trial is being conducted in collaboration with the UNISEC consortium. The research has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602012. Positive preliminary safety results were announced in November 2016. BiondVax’s consortium partners are continuing to analyze study samples. BiondVax expects the consortium will finalize and release results in Q2 2017.