Company Visits – RNAi coming to life

A special theme this trip was RNAi technology. We had meetings with the management of Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, both companies focused on RNAi based drug development.

RNAi or RNA interference utilizes a built-in defense mechanism in human cells against foreign genetic material. When such foreign gene coding molecules enters the cell, the molecular RNAi defense system recognizes the foreign material and destroys it. In its therapeutic use, the RNAi machinery is tricked into recognizing one of the body’s own disease-causing genes as foreign as subsequently stops those genes from being expressed (see figure below). This way selected genes can be effectively silenced and this biotechnological approach has shown promise in treating a wide array of different diseases, with the first RNAi drug hitting the market in 2018.

Alnylam is the pioneering company in the development of RNAi drugs. The company recently launched the first approved drug in a rare disease, and another drug candidate is geared up towards approval soon in another rare and debilitating disorder. Adding to that, Alnylam were the originators of a drug in late-stage development now run by another biotech company treating high cholesterol that affects millions of patients worldwide. What’s more, Alnylam’s clinical pipeline extends to several more potential treatments within many therapeutics areas.

Dicerna is the new kid on the block with an RNAi technology platform similar to Alnylam’s. While Dicerna’s pipeline is not as mature as Alnylam’s, a program treating a rare metabolic disorder has produced promising trial results to this point and may not be far from approval during the following year. Dicerna also has a wide early-stage pipeline where the company has teamed up with larger pharma companies such as Eli Lilly and Boehringer Ingelheim to address additional disease areas where RNAi technology can substantially move therapeutic goals posts.

Rare disease drug developers, big and small

Vertex Pharmaceuticals has become a biotech giant with a market value over USD 40 billion on the back of building a very successful franchise in treating patients with cystic fibrosis, a severe and debilitating congenital disorder. Cystic fibrosis most notably affects the respiratory system and significantly reduces patient’s breathing capacity. Vertex was the first company to successfully develop a treatment that targeted the underlying biochemical aspects of the disease for a subset of cystic fibrosis patients. The company also showcased its very promising development pipeline to replace their first generation drugs and to expand the therapeutic use to virtually all patients with cystic fibrosis.

We also met with the CEO of Albireo Pharma. This small cap company primarily develops new treatments for rare liver diseases that often affects children. Albireo has presented strong evidence of effect in a Phase 2 trial in one such liver disorder and are expecting confirmatory trial data to bring in front of regulatory agencies within a year.  What’s more, Albireo is building on its initial success by expanding development into more related rare liver diseases that can be targeted by the same approach. Plus, the company is growing an additional pipeline of novel programs to treat other liver-mediated diseases.

New ways to fight cancer

In the meeting with Agios Pharmaceuticals, we saw an example of the typical way we believe cancer treatments are heading in order to make a real impact for patients. Agios has developed two treatments for leukemia that relies on the cancer’s genetic makeup. If a patient is carrying particular cancer mutations, Agios’ matched treatments has shown considerable therapeutic effect that led to market approval, and now, new clinical trials to show increased effect of the drugs by combining them with other cancer drugs. In addition, Agios are also developing other cancer treatments and drugs to treat other hematological disorders.

Opportunities and challenges within central nervous system disorders

Sage Therapeutics has been a remarkable story as the company has challenged current treatment standards in depressive disorders, a therapeutic area were very little innovation has happened in the last decades. First, Sage was the first company to ever get approved in treating women suffering from post-partum depression (severe depressive episodes following child birth). Then the company took a swing a major depressive disorder, with an oral pill that has shown impressive effects so far in clinical development. Most importantly the anti-depressive effect of Sage’s drugs have much quicker onset than established drug to treat depression. 

We also paid a visit to the big biotech company Biogen that are now facing an overhaul in its product portfolio and development pipeline. This follows negative trial outcome for their front-running drug candidate in Alzheimer’s disease, where sadly no new treatment has been able to show noteworthy ability to halt disease progression. Biogen is also facing patent expiries in its large multiple sclerosis business and competition from a new gene therapy to its drug treating the rare muscular disorder SMA. For Biogen now, the key is pipeline hits to rejuvenate the company’s leadership role in multiple sclerosis and effective business development to bring in new programs in order to lead the future growth of the company.

A world leading hub for life science innovation

In Cambridge we met with Dr JC Gutierrez-Ramos, member of our Advisory Board, and CEO of Cogen Therapeutics, Dr Lovisa Afzelius, Chief Operating Officer at Cogen Therapeutics and Dr. Anthony Coyle, CEO of Pandion Therapeutics. Obviously the combination of rich access to seed funding and highly educated and skilled people from Harvard Medical and MIT are important pillars when building new companies based on disruptive innovations. Moreover, the very important culture with entrepreneurship and drive coupled with a unique infrastructure with large biotech and pharmaceutical companies make this area very special.

Dr. Gutiérrez-Ramos has over 20 years of drug discovery and development experience from leading global biopharmaceutical companies. Previously, he served as Group Senior Vice President and global head of the BioTherapeutics Research at Pfizer where he was responsible for more than 25 novel programs across the full spectrum of clinical development, re-launched efforts in Rare Disease Discovery and Development and founded the Centers for Therapeutic Innovation. He also oversaw and enhanced the biologics platform for the company from early discovery to entry in manufacturing. Before that, JC was Senior Vice President and Head of the Immuno-inflammation Center for Drug Discovery at GSK, where he founded entrepreneurial units such as Epinova and Tempero focused in translating novel areas of science into therapeutics. He began his career in the drug industry at Millennium Pharmaceuticals serving as Vice President of Inflammation Drug Discovery. During his academic career he was part of the Faculty at the Genetics Department of Harvard Medical School and the Basel Institute for Immunology in Switzerland. Dr. Gutiérrez-Ramos holds a Ph.D. in immunochemistry from the Autonoma University in Madrid, Spain.

 


Arctic Aurora LifeScience is an equity fund investing in global biotechnology and pharmaceutical companies. The fund is run by former portfolio manager in the Swedish Governmental Pension Fund AP3, Ulrica Bjerke, as well as Dr. Torbjørn Bjerke, both with 20 years of experience from the market. Arctic Aurora LifeScience was launched in May 2016 with both hedged and un-hedged share classes.

Past performance in Arctic Aurora LifeScience is no guarantee for future returns. Future returns depend on the market, fund manager skill, fund risk level, costs, among others. Performance in the fund may at times be negative and may for this fund vary considerably within periods.