Interview: Oryzon Chief Highlights CNS Opportunities
Executive Summary
After the setback of Roche pulling the plug on a potentially lucrative cancer partnership last year, the Spanish biotech tells Scrip it has bounced back with a compound that shows potential in Alzheimer's, multiple sclerosis and other neurodegenerative and psychiatric diseases.
Oryzon Genomics SA, one of the leading lights in the Spanish biotech sector, hopes that with vafidemstat, it may have a molecule that can be a 'pipeline-in-a-product' to serve as a treatment for a wide range of central nervous system (CNS) diseases.
Speaking to Scrip at the BioSpain meeting in Seville last week, Oryzon CEO Carlos Buesa said that in the past three years the company had made "immense progress" with vafidemstat, an oral and brain penetrant drug that selectively inhibits two enzymes: lysine specific demethylase 1 (LSD1) and monoamine oxidase B inhibitor (MAOB). A number of mid-stage trials are underway, with a lead program in Alzheimer's disease.
Buesa focused on a "very ambitious" Phase IIa study which is recruiting 150 patients in four countries – Spain, the UK, France and the US - to evaluate the safety and tolerability of vafidemstat , also known as ORY2001, in patients with mild and moderate Alzheimer’s. The study "has been designed very carefully," he claimed, with secondary endpoints including memory and behavior alterations, plus monitoring the variations of diverse cerebrospinal fluid (CSF) biomarkers.
Stressing that the trial is complex, Buesa said that rather than focusing on statistically significant efficacy, "we are looking for signals so that we can design a Phase II/III trial." In preclinical studies, vafidemstat not only restores memory but reduces the exacerbated aggressiveness of mice to normal levels and also reduces social avoidance and enhances sociability.
Buesa also made reference to two other ongoing studies of vafidemstat that are "different in magnitude and ambition." First up is a Phase IIa study evaluating the drug in patients with both the relapsing-remitting and secondary progressive forms of multiple sclerosis.
While many people may argue that MS is "absolutely covered," Buesa said the vast majority of therapies for the disease "are just delaying progression." There is a lot room to improve research in the space, he added.
The third vafidemstat Phase IIa study is a 'basket' trial in patients with episodes of aggressiveness in two neurodegenerative diseases (Lewy body dementia and Alzheimer's) and three psychiatric ones (autism spectrum disorder, borderline personality disorder and adult attention deficit hyperactivity disorder). The trial, which Buesa said is "a very elegant concept" normally seen in oncology studies, will include six patients per indication and will be conducted at the Valle de Hebrón hospital in Barcelona.
If all goes well, Oryzon hopes that rather than being perceived purely as a potential Alzheimer's candidate, vafidemstat can be turned into a franchise in the CNS field, Buesa said. Investors certainly have high hopes for the company, which relocated its head office to Madrid from Barcelona days after a controversial unofficial independence referendum was held in Catalonia in October last year; its stock has risen 40% since the beginning of 2018 and has climbed over 105% in the past 12 months.
This represents quite a turnaround for the firm, which describes itself as "the European champion in epigenetics" but suffered a major blow last July when Roche pulled the plug on a potentially lucrative partnership that was developing a LSD1 inhibitor code-named ORY-1001 and now called ladademstat for acute myeloid leukemia (AML) as well as solid tumors.
Buesa told Scrip that there are three main reasons why an asset is returned. "It maybe safety concerns but that was not the case, or efficacy concerns, that was not the case, or portfolio prioritization, which was the case." He said that big pharma "has so many plates on its table and if you don't have an internal advocate, for very legitimate reasons they are going to spend their dollars elsewhere."
He said "we were really not expecting this and it was a great pity as Roche was a magnificent partner." However, "what we felt a year and a half ago to be a setback we now see more as an opportunity." Last month, the company received approval from the Spanish Drug Agency (AEMPS) to conduct a Phase IIa clinical study with ladademstat in combination with the standard of care treatment azacitidine in elderly AML patients not eligible for intensive chemotherapy.
On the business side, Oryzon, which listed on the Spanish stock exchange in December 2015 and has raised over $50m from blue chip investors in Europe and US in the past couple of years, has enough cash to fund operations to the beginning of 2020, Buesa said. He added that the company is "always scrutinizing the market" in terms of potential big pharma partnerships and future financing rounds; a Nasdaq listing is a target, although the firm is not giving any timeline for that.
Buesa concluded by saying that the Spanish biotech sector is in rude health. Although "there is a kind of shyness when we compare ourselves to the US and we operate on a smaller scale, we have stellar science and a lot of talent in Spain in terms of scientific and managerial skills which is increasingly being recognized abroad." (Also see "Spanish Biotechs Prepare To Seek Partners In Seville " - Scrip, 20 Sep, 2018.)