The newly founded SynOx has become the latest startup to attack solid tumors via their ‘comfort zone’, known as the tumor microenvironment.
SynOx was spun out of the UK firm Celleron Therapeutics last week with a huge Series A round of €37M. The fledgling company is developing an antibody drug that Celleron licensed from Roche in August to treat a rare form of cancer in the joints called diffuse tenosynovial giant cell tumors.
SynOx’s candidate drug is designed to deplete a type of immune cell called macrophages close to the tumor. These cells normally function as fighters against foreign pathogens, but those close to cancer cells are sometimes hijacked and used to suppress immune cells.
The drug falls outside of the two broad camps of traditional cancer treatments: those that kill cancer cells directly, and those that boost the immune system’s natural ability to destroy cancer cells. Instead, it is in an emerging group that remodels the tumor microenvironment — the unique conditions within and surrounding tumors that nurture and protect the tumors from immune cells.
“There are still many cancers that remain largely unresponsive to currently available therapies, so new asset classes with novel mechanisms of action are badly needed for such hard-to-treat tumor types,” said Tim Skerry, co-founder and CSO of the UK company Modulus Therapeutics.
So far, there are no treatments in the market designed to rewire the microenvironment. However, some approved cancer immunotherapy drugs could be partly working this way such as Bristol Myers Squibb’s antibody drug ipilimumab.
The last five years have seen a growing movement of pharma and biotech companies intentionally targeting the tumor microenvironment. In the last year, this trend seems to be getting stronger.
“It’s an emerging field and one that holds great potential for the future,” Skerry said. “We’re really only beginning to understand the key components of the tumor microenvironment and how it supports and nurtures tumor growth.”
Skerry’s company, Modulus Therapeutics, was spun out from the University of Sheffield in September to tackle the tumor microenvironment in solid tumors such as pancreatic and breast cancer. The company is developing a drug that blocks the action of adrenomedullin, a hormone sometimes co-opted by tumor cells as a communication tool.
“We are looking at a very particular mechanism that impacts not only directly on cancer cell growth but also on the way the cancer communicates with its immediate environment,” Skerry added.
Also in this field, the Swiss Polyphor licensed its breast cancer candidate balixafortide to the Chinese giant Fosun Pharma for up to €154M ($182M) in late August and the US companies Gilead Sciences and Jounce Therapeutics formed a licensing deal in September.
“It’s kind of picked up in the last five years, constantly evolving,” said Arnaud Foussat, Operating Partner at Advent France Biotechnology. “It is moving fast.”
Foussat leads two French biotech startups that focus on breaking through the tumor’s protective microenvironment. The first is the Star Wars-inspired Alderaan Therapeutics, which raised an €18.5M Series A in January to take its cancer drug to phase I in 2022. The company’s antibody drug is designed to block immunosuppressive T cells in the tumor microenvironment called regulatory T cells.
The second company run by Foussat is Yukin Therapeutics. The French startup raised €3.3M last year to fund the preclinical development of small molecule drugs that could stop the growth of solid tumors and reprogram their microenvironments to allow the immune system inside the tumor.
A very recent offshoot of the tumor microenvironment field also aims to destroy solid tumors that hack into nearby neurons as communication tools in their microenvironments. For example, the UK startup Divide and Conquer, founded last year, aims to apply this cancer research to brain tumors such as glioblastomas.
The last few years have seen the rise of checkpoint inhibitor drugs to treat cancer by releasing the brakes that tumors place on immune cells. But their limited benefits for certain patients has meant treating solid tumors relies more and more on combination treatments.
“You can combine different treatments and really get a potentially huge synergy in the treatment of immune responses,” said Foussat.
Targeting cancerous tumors in their comfort zone could free the immune system from their dampening influence. This could extend the boundaries of current cancer immunotherapies and greatly boost their usefulness going forward.
This is an updated version of an article published on the 16th of September, 2020
Images from Elena Resko and Shutterstock