Special Startup Series: The quest for safer cancer cure

Pune based biotech startup, CyCa Oncosolutions is working on an indigenous drug delivery system that could target only cancer cells without any damage to adjoining tissues, eradicating the painful side effects and thus improving the quality of life of cancer patients

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Cancer, as we know, is one of the most dreaded diseases in the world. What makes it worst is the fact that the course of treatment itself leads to trauma and suffering for patients due to chemotherapy.

Therefore, scientists have been trying to find alternative routes of treatment for the disease. In India too, there are many researchers who are using varying methodologies to arrive at a solution. In that context, working on a bio-based solution is a startup, Cyca Oncolutions that is focusing on a drug delivery system which ensures that the drug doesn’t cause any side effects. The company was founded in Bhubaneswar, Odisha by Dr Nusrat J M Sanghamitra during February 2017 and now operates from Venture Centre incubator at National Chemical Laboratory, Pune. The entire journey from Bhubneshwar to Pune is quite interesting.

Nusrat did not venture into the world of entrepreneurship in a conventional way with a business idea. For her, entrepreneurship was not a mere career option but a way of life. Right from an undergraduate degree, she was inspired by the idea of finding a better drug for cancer in her own naïve and often unconventional way! Incidentally, while she was doing PhD, her father was diagnosed with cancer and is still under medication. This whole experience has kept her going so far and also provided her with a mission to accomplish.

During the course of her PhD, Dr Nusrat synthesized a series of Cu(I) Phosphine complexes and looked into their anticancer activity. However, the lead molecule based on the in vitro results was extremely toxic in vivo. Disheartened by that, she felt that there was a need to understand the mechanism of action of the drugs. Since most of the drug targets were proteins, she wanted to study protein structure and function.

“It was at the same time, Prof. Mazumdar in TIFR accepted me and taught me protein engineering. The following few years of work was not directly relevant to anticancer drug research but I enjoyed studying the biophysical chemistry of proteins and protein functionalization” says Nusrat whose eureka moment was the serendipitous discovery of a novel mechanism of cell entry of a protein (it was originally engineered to explore its potential as a nanoreactor) during her tenure in Kyoto University.

During these years, she was kind of convinced that there are enough of cytotoxic drugs and issue was that there is an absence of the right fit or how to make them work. She also needed to reduce the dosage of such drugs. Based on that discovery, she developed a hypothesis and used her PhD work to prove the hypothesis.

Inception

Not convinced to continue research as a faculty member in a research institute, Nusrat took a break year and went for volunteering in school, in palliative care organizations and went to Jordan to do an intensive course in Arabic.

During this period, Mr M. Nikhil (Program Manager) and Dr Mrityunjay Suar (CEO) of KIIT Technology Business Incubator convinced her to apply for the Biotechnology Ignition Grant (BIG) from BIRAC, as the scheme offers 50 lakhs to come up with a proof of concept in 18 months.

“It was exciting though I was apprehensive, as the idea was very risky. But thanks to BIRAC for believing in the concept and giving me the grant,” she says.

That was the beginning of CyCa Oncosolutions’ entrepreneurial journey. The company that was conceptualized and initiated in Bhubneshwar finally found its roots at Venture Centre in Pune during October 2018.

The first funding support for Cyca Oncosolutions had come from BIRAC’s Biotechnology Ignition Grant. During the later course of its journey, the company also managed to raise funds from many sources, including equity-free seed funding from BIRAC and BPCL, equity-free prize money, including the President of India’s National Tech Startup Award, TiE-BIRAC WiNER award, RICH Cancer Innovation Challenge Award and Enterprise Ireland New Frontiers phase II scholarship. It has also raised equity investments through the Rebel Bio Accelerator and SOSV, Ireland).

Challenges

“CyCa Oncosolutions celebrated two years on February 2019. I think I have been lucky and blessed that everyone found the technology very promising, and even in the initial days, I found funding from BIRAC, BPCL and SOS Ventures. Incubators like KIIT TBI, Bhubaneswar and Venture Centre Pune played a great role in getting access to the equipment whenever it was needed,” says Nusrat who is thankful to Prof. Shyamalabha Mazumdar for giving her access to his laboratory for a month in TIFR, Mumbai to get the initial work done.

She has a long list of people she wants to say thanks to. “I have been lucky to get help from mentors from BIRAC, KIIT TBI Bhubaneswar, Venture Center Pune, SOSV, Ireland and New Frontiers Program, Rubicon Centre, Ireland, she says adding “In addition to the wonderful teams from each of these organizations, I would like to specially mention a few people, who I can write to at any time to ask for advice: Dr Renu Swarup, Dr Satya Dash, Dr Shriram Raghavan, Dr Mritunjay Suar, Dr Premnath, Prof. Anil Gupta, Mr Bill Liao, Mr Liam Fitzerald, and Ms Sally Hudson.

However, the real challenge for the company begins now. It has to generate the next level of data, so that it can continue raising further investment and receive continued support. For Nusrat, the biggest challenge so far has been building her team, where she needs to find and retain skilled people within a limited budget.

Novel R&D work aimed to capture a big-ticket market

The R&D work at the company is based on a novel engineered protein USG (Universal Sliding Gateway). USG is a proprietary engineered molecule (International Publication Number WO 2019/038344 A1) that works just like a molecular drill: it can bore into the cell and deliver drugs into it without causing any harm to the cell, solving the most crucial issue of intracellular delivery and lowering dosage by up to 90%.

USG is to the cell what a USB is to any computer. It’s a system that allows safe transferring of (biological) information, and thus its applications are not limited to oncology, but expand also into superbug control, Car-T applications and even as an in-vivo gene editing toolbox for Cas9 as a one-shot gene therapy tool and research reagent for live cell imaging.

In terms of product development, Cyca Oncosolutions is in the post POC stage. So far, it has proven the POC in an in-vitro cell model. The 14 days safety trial in mice has been completed and now the team is carrying out experiments on immunogenicity and 3 months toxicity trial in mice. Since licensing deals is one of its possible commercialization strategies, the company is looking to reach that level by 2021.

The prime focus of the company is anticancer drug market, which has a total addressable market (TAM) size of $ 75-80 billion, and out of that, the service obtainable market is $ 3-4 billion. In our other two verticals, i.e., in antimicrobials, the company is addressing a service obtainable market of $ 840 million out of the (TAM size $ 60-70 billion), and in the research reagent market, it is $ 292 million (out of the TAM of $ 9 billion).

“At this point, given that our business model is non-exclusive licensing in multiple segments, we can only forecast revenues by analyzing past deals. So if we successfully obtain all pre-clinical results as envisaged, the following are the numbers forecasted by assessing last 10 years of licensing deals in the space of drug delivery device platform technology,” explains Dr Nusrat.

Way Forward

The CyCa OncoSolutions’s business model is to take its formulations till the pre-clinical stage and timeline to reach this stage is the end of 2020. The company will go for a co-development partnership with a big or mid-sized pharma company or license the technology in one or more ways by 2021. These include R&D by Contract Development and Manufacturing Organizations (CDMOs); Out-licensing USG (non-exclusive) to leading pharma companies and/or JDA (Joint Development Agreement); Strategic collaborations to out-license USG-drug conjugates and sell the USG-drug formulation for pet (dog/horse) therapeutics.

The company is currently looking to raise more funds to support its GLP grade pre-clinical trials.

While Dr Nusrat is extremely appreciative of government support, she has few suggestions. She says: “I can’t imagine getting this far if BIRAC’s BIG grant would not have been there. However, there are more needs when technology requires multiple high-end equipment. Incubation charges can be cheaper to help startups achieve more milestones within a limited budget, especially for pharma/biotech startups where the gestation period is too long!”

For Dr Nusrat, the sky is the limit. She on a highly optimistic note says that if the technology works as envisaged and the preclinical safety and efficacy studies are successful, she would like to lead CyCa OncoSolutions through its growth phase into a globally recognized public pharmaceutical company.

“I would like to see an improved quality of life for cancer patients as a result of the novel formulations developed by Cyca Oncosolutions,” she says.

Our best wishes to the resolve of the founder and her team.