Oblique Therapeutics: Uncovering Medical Breakthroughs in Antibody Therapeutics

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Owe Orwar, CEO, Oblique TherapeuticsOwe Orwar, CEO The biotech and pharma industries are constantly working towards new technological advancements ranging from smart medical devices, clever small molecule approaches, novel biologics-based treatment paradigms, AI implementation, and smart big data integration to satisfy patient needs and be meaningful. There is a more outspoken need for innovation across the board where patient groups, governments, payors, regulatory agencies, and clinical professionals are vocal about the need for change and demand increased productivity of high-quality new medicines from biotech and pharma companies. They do not want to see just more of the same or incremental innovation; they want to see a real change towards effective and better medicines. Understanding the need of the hour, Oblique Therapeutics a curiosity-driven, innovative biotech company, follows an approach to generate meaningful novel antibody therapeutics for the benefit of patients. With its proprietary Abiprot technology, the company is developing antibodies against difficult-to-drug targets such as ion channels and certain G-protein-coupled receptors (GPRs) that can translate into new effective treatment options for large groups of patients in need of new medicines. “We are focusing on advancing a pipeline of new antibody therapeutics in the pain therapeutic area and advanced metastatic cancer. No one has done it before, and it would open avenues for novel treatments of a broad spectrum of diseases that today are difficult or impossible to treat,” says Owe Orwar, CEO of Oblique Therapeutics.

As a patient-centric company in the deepest meaning of the term, Oblique Therapeutics is geared toward helping as many patients in need as possible, independent of disease or therapeutic area, with new breakthrough medicines that matter. The company do not do me-too’s, biosimilars or incremental innovation. Instead, it is pragmatic and result-driven, propelled by the promise of the Abiprot platform. “While it is true that we are specialising in pain and cancer, but if we can satisfy unmet medical needs in any other area, and have convincing evidence that our platform can deliver efficacious antibodies, we will try to do it,” says Orwar. The company is working exclusively with diseases which have been considered difficult-to-target, for large patient populations.

The platform technology was developed during Orwar’s time as a Professor at the Chalmers University of Technology, together with Carolina Trkulja, who was a PhD student at the time. Currently, she is serving as the co-founder and Chief Scientific Officer at Oblique Therapeutics. Both of them developed and validated the platform for antibody discovery, and went after two “hot” drug targets where there had been multiple unsuccessful attempts to develop drugs against. The first was the TRPV1 ion channel which was clinically validated in acute and chronic pain, and the second was the oncogenic mutated KRAS, a small GTP:ase, highly relevant in aggressive and metastatic cancer. “After generating early but promising results for both of these targets, we decided to secure the IP and commercialise the technology and founded the company in 2015.

While it is true that we are specialising in pain and cancer, but if we can satisfy unmet medical needs in any other area, and have convincing evidence that our platform can deliver efficacious antibodies, we will try to do it

Very soon, we initiated collaboration with big pharma adding two different diabetes type 2 targets to our pipeline,” mentions Orwar.

Developing Antibodies for Difficult-to-Drug Targets

Oblique Therapeutics develops antibodies using its proprietary platform technology Abiprot as well as its target selection algorithm, Abiprot Select. As a proteomics-and-bioinformatics-based tool, the Abiprot platform identifies high-affinity antibody binding sites in any given protein with a single amino acid resolution using a tailored molecular reporter system. The platform yields detailed sequence and structure information for epitope development directly from native proteins. “In some instances, we can also control the pharmacology of our antibodies by careful selection of epitopes to yield either antagonistic or agonistic antibodies,” says Orwar. Abiprot works well with both soluble and membrane-bound proteins, with a focus on epitope discovery in ion channels and G-protein-coupled receptors. An additional advantage with this approach is the generation of relatively small panels of high-quality antibody leads and can advance into lead optimisation in a very short period of time.

On the other hand, Abiprot Select is an algorithm or set of rules for target selection that is optimised to harmonise with the antibody discovery platform. The algorithm is designed to eliminate risk and significantly reduce cost and development time. To achieve this, the first criteria is that the target must either be clinically validated or have compelling evidence of efficacy from human genetics studies. Thus, selected targets are typically those that have been tried with small molecules and met efficacy endpoints in a phase 2b or later study but failed overall due to toxicity and SAEs. Another rule is that the company should have convincing evidence that these targets can be addressed with an antibody approach. Typically, Oblique Therapeutics saves millions of dollars in research and development and 5-10 years of time compared to starting out a program with a novel uncharacterised target.

Creating Novel Treatments Targeting ION Channels and GPRs

Currently, Oblique Therapeutics’ pipeline consists of 6 programs, of which three are run in collaborations with pharma companies to co-develop antibodies. Oblique Therapeutics is working in collaboration with big- and medium-sized pharma companies on different targets relevant in metabolic disease and pain, respectively. “In all three cases, we have generated small panels with antibody leads that are currently being tested. Two of the targets are ion channels, and one is a GPR, so it is really exciting to see how they will perform.” The company also has a small molecule anticancer agent called OT-1096 in its pipeline.
OT-1096 is an anticancer agent that locally activates an immune response in the tumour microenvironment showing promising results in preclinical models using cancer-bearing humanised mice. “We are planning to start a phase 1 clinical study in triple-negative breast cancer within 18 months or so,” adds the CEO. The company intends to use OT- 1096, next-generation small molecule immunomodulator to target advanced metastasised triple-negative breast cancer. Apart from TRPV1, KRAS, and the two diabetes antibody programs, Oblique Therapeutics just recently added leads for TRPA1, which is structurally related to TRPV1 and is also of great interest in acute and chronic pain settings.

Similarly, the company’s pipeline will have a focus on developing novel treatments in chronic pain because of the perfect match between patient needs, platform capabilities, and clinical understanding. Given the problems around current analgesic medicines, the opioid crises, and the huge unmet medical need, Oblique Therapeutics has found a niche area with the promise to develop novel antibody medicines towards pain targets that are almost exclusively ion channels. “With our Abiprot platform, we feel confident that we have a reasonable chance to a breakthrough, and since we see the opportunity, we are obliged to explore it in the interest of patients,” notes Orwar.

Looking toward a Promising Future of Medication

The driving force and the guiding light of the company, Orwar brings almost two decades of experience in the fields of biotech and pharma. He has developed a strong global understanding of the pharma market, including diabetes and oncology care, ranging from new targets to commercial operations, as well as the strategic approaches taken by different companies across the world. In his efforts, he is powered by a dynamic team with mixed backgrounds from big pharma, biotech, and academia. The team consists of persons with more than 20 years of experience from the industry with several marketed drugs in their CVs and younger talent with strong scientific and entrepreneurial spirits. “Together, we form a team with a solid scientific background and an agile, innovative mentality running and expanding the company together with its many international collaborators,” explains Orwar.

"We are focusing on advancing a pipeline of new antibody therapeutics in the pain therapeutic area and advanced metastatic cancer"

With a stellar team, Oblique Therapeutics opened new offices in Stockholm and is constantly looking for brilliant individuals. Adjacently, its platform technology is continuously being improved by adding new targets and antibodies to its pipeline. “Our goal is to take on five new targets a year, and primarily expand in the pain field but also looking into other targets that fit our selection criteria,” remarks Orwar. Since the company’s platform technology has proven to produce antibodies with high selectivity, high-affinity, and sometimes with programmed and complex pharmacology, Oblique Therapeutics is all set to continue to explore new targets. With the aim to continue on the novel idea to advance antibody discovery and development for currently undruggable but clinically important targets, Oblique Therapeutics is working toward bringing real medical breakthroughs to the industry.
- Kenneth Thomas
    July 12, 2019