Landos Leverages Advanced Computing For Autoimmune Disease Drug Development
Executive Summary
Emerging Company Profile: Start-up Landos is raising money through a Series B financing to fund Phase II development of its lead oral, gut-restricted compound and described its plans in a video interview at the Biotech Showcase in San Francisco in January.
Resting on a backbone of drug development shaped by advanced computing, start-up Landos Biopharma Inc. is developing first-in-class oral drugs for autoimmune diseases, starting with its lead compound BT-11 for Crohn's disease.
The Blacksburg, Va.-based company was founded in 2017 as a spin-off of Biotherapeutics, which specializes in advanced computational modeling for development of personalized therapeutics.
In 2010, Biotherapeutics received a $12m grant from the National Institute of Allergy and Infectious Diseases (NIAID) to fund the building of a mathematical/computational system for modeling of immunity for biodefense purposes.
Landos Biopharma
Location: Blacksburg, Va.
Founder: Josep Bassaganya-Riera
Founding Date: 2017
Financing: $10m from Perceptive Advisors
Disease Area: Crohn's and ulcerative coloitis
R&D Focus: Oral, locally acting drugs for auto-immune diseases
Patents: Composition of matter and method of use patents through 2035
Management Team: Josep Bassaganya-Riera (CEO); Raquel Hontecillas (CSO); Andrew Leber (Scientific Director); Chris Garabedian (Senior Business Advisor)
Board of Directors: Josep Bassaganya-Riera; Chris Garabedian Clinical Advisory Board, IBD: Francisco Sylvester (CCFA); Fabio Cominelli UH Case Medical Center; William Sandborn (UCSD); Jean-Frederic Columbel (IBD Center, Mount Sinai); Maria Abreu (University of Miami)
Employees: 18
The technology is agnostic and may be applied to a range of disease areas, although Landos was established with a focus on applying the IT infrastructure in autoimmune disease.
CEO Josep Bassaganya-Riera noted in an interview that the predominant drugs in autoimmune disease today are – unfortunately, he said – biologics that target a specific cytokine and neutralize it. The problem is that if you take one cytokine out of the equation there are three, four, maybe even 10 others that can take its place
"Then people are surprised when biologics work in about 30% or 40% of patients and have this side effect profile which is horrible – cancer, infection and death – so there is clearly an unmet need. And new approaches are needed, new mechanisms of action, new procedural approaches to tackle that otherwise intractable problem," the exec said in an interview at the recent BIO Investor Forum.
With traditional immunology research, a component is taken out of the network as a whole and there is hope for a good result, whereas Landos' approach is to use advanced computational systems for a comprehensive, systems-wide understanding of the immune system, in the gastrointestinal system for Crohn's disease and ulcerative colitis, in the pancreas for type 1 diabetes, the brain for multiple sclerosis or joints for rheumatoid arthritis.
"We are understanding what is wrong, what is dysregulated, not only considering a subset of cytokines but the overall network. This technology is helping us making us decisions on experiments that we need to run more efficiently. It's helping us cut costs and adding overall efficiency in the preclinical stage," Bassaganya-Riera said.
The company was financed through a $10m Series A round that exclusively involved life sciences management firm Perceptive Advisors in New York.
The company has 18 employees and uses about 40 consultants. "We wanted to be very lean at this early stage," Bassaganya-Riera said.
Financing Phase II For Crohn's And Ulcerative Colitis
The plan is to advance a pipeline for autoimmune diseases in partnership with Xontogeny, a Boston-based life sciences accelerator company led by Chris Garabedian.
Landos' lead candidate BT-11 is an oral, locally acting drug that binds Lanthionine Synthetase C-Like 2 (LANCL2) to increase anti-inflammatory molecules, including IL-10 and FOXP2, and reduce pro-inflammatory markers, including MCP1, TNF-alfa and interferon gamma, in immune cells within the GI tract.
The drug is being targeted at inflammatory bowel diseases, which affect some 1.6m people in the US and 4m worldwide.
In animal studies, BT-11 decreased gut inflammation by 90%. Phase I studies of BT-11 have been completed and showed no dose-limiting toxicities and a wide safety margin. Top-line results from a Phase I trial of healthy volunteers were released on Jan. 7. In addition to being well-tolerated and safe, the drug was associated with a reduction in fecal calprotection, which could represent an anti-inflammatory signal, Bassagany-Rivera explained in an interview at the Biotech Showcase, which is held in San Francisco in parallel with the J.P. Morgan Healthcare Conference.
The company said it is currently looking to raise $60m in a Series B round to fund Phase II studies of BT-11 in Crohn's disease and ulcerative colitis and to advance several other clinical candidates in its pipeline to IND stage and Phase I in 2019. Landos has six other assets in preclinical development, including BT-15 for type 1 diabetes and BT-13 for rheumatoid arthritis.
Bassaganya-Riera acknowledged that challenges in development include access to patients for trials as the exclusion criteria in Crohn's studies limit the pool of those eligible to take part – in some Crohn's disease studies the recruitment rate per site is 1.2 to 1.5 patients per year. The company expects that it will need 70 to 80 trial sites, including in the US and Europe.
Landos' employee count will grow a bit after the Series B, but the company does not anticipate significant growth until the time of an initial public offering, planned for the first half of 2020.
The company expects to be ready to file an NDA by 2024 and is open to a range of exit possibilities, including M&A or a strategic partnership.
Keeping Track Of The Competition
Bassaganya-Riera is monitoring competing oral approaches in development but believes Landos' candidate has advantages.
Johnson & Johnson has been partnered with Protagonist Therapeutics Inc. on the oral peptide therapeutic PTG-200, which targets interleukin 23 (IL-23) for a range of indications including Crohn's and ulcerative colitis since May 2017, through a deal that included $50m up front and up to $940m in milestone fees and double-digit royalties. (Also see "Janssen Enriches Crohn's Portfolio In Deal For Protagonist's Oral IL-23 Inhibitor" - Scrip, 30 May, 2017.)
Bassaganya-Riera said he is skeptical about this and similar approaches because the GI tract is designed to destroy peptides. A small molecule has a better chance of getting the job done because "you are not going up against evolution," Bassaganya-Riera said.
Celgene Corp.'s oral Smad7-targeted oligonucleotide-based drug mongersen failed in Phase III and more and more it is looking like the drug didn't meet endpoints because not enough of the drug got to the distal parts of the colon, the exec said. (Also see "Celgene IBD Pipeline In Question As Mongersen Crohn’s Disease Trial Ends" - Scrip, 20 Oct, 2017.)
J&J has also been also partnered with Theravance Biopharma Inc. for the oral, intestinally restricted pan-Janus kinase (JAK) inhibitor TD-1473 for inflammatory bowel disease in a February 2018 deal that included $100m payment and could be worth up to $1bn. (Also see "Theravance Banks $100m As J&J Bets Big On IBD Drug" - Scrip, 7 Feb, 2018.)
However, as with biologics that are used as part of the standard of care, JAK inhibitors are associated with immune suppression, which raises the risk of cancer, infection and death, the exec said.
Landos will continue to closely monitor development activity of oral, gut-restricted drugs in inflammatory bowel disease, he added.