Orum Ascending High Mountain Of Undruggable RAS Protein
Executive Summary
Emerging Company Profile: Orum Therapeutics is aiming to develop a first-in-class therapeutic antibody for cancer and other intractable diseases, using its unique cell-penetrating antibody platform. Following a successful Series A financing, the young South Korean biotech’s next big milestone is to enter clinical trials by 2019 with its first program in oncology, targeting activated RAS protein.
Formerly the head of research, Asia Pacific R&D, at Sanofi, Sung Joo Lee, CEO and co-founder of Orum Therapeutics Inc., has long been interested in innovative novel drug research and has been searching for platforms that can address undruggable targets.
He found an interesting prospect in research at South Korea’s Ajou University and proposed Professor Yong Sung Kim - leading expert in antibody engineering, especially cell penetrating antibodies - to establish a biotech start-up. That was how he became co-founder of Orum Therapeutics in August 2016, a venture that has exclusively acquired intellectual property from Ajou University covering cell-penetrating antibodies.
“Many patients are suffering from undruggable targets, but there aren’t particular alternatives. I have been closely eyeing the platforms that can address them,” he told Scrip.
From the beginning, Orum Therapeutics has largely attracted the industry's attention thanks to its unique platform that appears to be the only cell-specific cell penetrating antibody platform in the world. Orum leverages its platform to inhibit drug targets undruggable by small molecule or current antibody therapeutics.
Targets, Lead Project
Its first program RT11-i, a novel monoclonal antibody, is designed to be internalized by the cell and to directly target the activated form of RAS. The data published in Nature Communications shows that RT11-i binding is specific to activated RAS, binds these proteins inside the cell and blocks interactions with effector proteins, and results in inhibition of downstream oncogenic signaling.
When given to tumor-bearing mice, RT11-i inhibited tumor growth in several xenograft models and was shown to be well tolerated.
The RAS gene family comprises the most commonly mutated oncogenes that are involved in about 30% of all human cancers, but have eluded drug discovery efforts for over 30 years.
“There are seven cancer initiatives in the US. The first one is the Cancer Moonshot, the second one the Precision Medicine Initiative, and the third is the RAS Initiative, which is the only initiative with the name of a protein target,” the CEO noted. “If this gets the FDA’s approval, it will be an event that will be written in a textbook.”
Orum Therapeutics Inc.
Location: Daejeon, South Korea
R&D Focus: Cancer, Severe Genetic Diseases
Disease Areas: Pancreatic, Colon, Non-Small Cell Lung Cancers, Neurofibromatosis 1
Founding Date: August 2016
Founders: Sung Joo Lee, Yong Sung Kim
Employees (number): 6
Financing Total to Date: $8m (Series A)
Investors: InterVest, KB Investment, Solidus Investment, LB Investment
RAS proteins function to transmit signals within cells that control cell growth, differentiation and survival, and mutations found in human cancers result in RAS being constitutively activated. In addition to playing a role in tumor formation, tumors containing activating RAS mutations are often aggressive and do not respond to current therapies, including drugs targeting EGFR such as Erbitux (cetuximab).
Despite its prominent role in human cancer, previous efforts to directly target activated RAS have failed to produce a therapy that works in humans.
“Mutant RAS protein has been considered a highly-validated cancer drug target, but also has a reputation as being undruggable," Lee said. "RT11-i described in our recent Nature Communications publication targets integrin-expressing cancer cells and inhibits activated RAS(RAS-GTP).
“This enables blocking of aberrant RAS activation caused by all activating mutations in KRAS, NRAS and HRAS. This is in contrast to approaches that focus on a particular KRAS mutations (G12C, G12D etc)."
First-In-Class?
Lee believes Orum’s technology has the capacity to create the first-in-class RAS-targeted therapeutic antibody for pancreatic, colon and non-small cell lung cancers with RAS mutations.
Inhibiting RAS is one of the “holy grails” of cancer treatment, and different teams are approaching this from various innovative approaches such as exosome-siRNA delivery, covalent inhibitors, cell penetrating biologics and small molecule PPI inhibitors, he said.
According to Biomedtracker, six different drug candidates targeting RAS were being developed as small molecules, two as cellular, two as peptides, one as antisense, one as viral and one as siRNA/RNAi.
Earlier this month, Orum successfully completed an $8m Series A financing with the participation of InterVest, KB Investment/Solidus Investment, and LB Investment. The proceeds will be used to support its first program in oncology targeting activated RAS protein.
“We were impressed with Orum’s cell-penetrating antibody platform, which can transform antibodies to effectively target undruggable cytosolic targets, without chemical conjugation and with target cell specificity,” said Yeo Jung Moon, Investment Division Director at InterVest, in a statement. “We look forward to providing our expertise and guidance as the company creates new treatments for cancer and rare diseases.”
Yeo Jung Moon, Investment Division Director at InterVest, will join Orum’s board of directors.
The next big milestone for the company is to begin clinical trials of RT11-I by 2019. The company hasn’t decided if it will conduct these studies in South Korea or overseas, Lee said.
Going forward, Orum remains open to different financial paths, such as further fund raisings or an initial public offering, to reach its goal of inhibiting RAS and treat other intractable diseases. It is also searching for partners with global patient access and expertise in antibody development to co-develop or license its cell penetrating antibodies, the CEO said.
From the editors of PharmAsia News.