Zumutor inches closer to crucial milestone for biotech startups from India

Cancer research requires a gritty chase braving tonnes of frustration and dead ends. So when a domestic biotech startup approaches an early milestone despite the odds, including a perennial funding winter for the sector, it demands attention.

Zumutor Biologics is among a new breed of biotech startups from India focused on immuno-oncology — treatment that boosts the immune system to fight cancer. What stands out about the company is its therapeutic focus on activating natural-killer cells, as opposed to the relatively more common approach of T-cell therapy.

Both are part of the immune system. But while T cells have to be primed to seek and target antigens on cancer cells, NK cells can be activated more innately to detect and respond to early signs of cancer, according to researchers.

Zumutor recently said it had received a positive pre-investigation response from the US Food and Drug Administration for its lead molecule, ZM008. Developed in Zumutor's lab, ZM008 is a monoclonal antibody (mAb) that enables NK cells to activate a potent immune response in patients of prostate cancer.

The biotech startup from Bengaluru is now on track to apply with the US FDA for a new investigational drug programme (IND) in the current financial quarter, said CEO Kavitha Iyer Rodrigues.

“We got a good response from (the US FDA),” Kavitha told YourStory. “They said the starting dose is good, as this is a MABEL (minimum anticipated biological effect level) approach, and you can go ahead to the next steps towards an IND filing.”

“The IND filing is the precursor to starting Phase I trials,” Kavitha added.

Headquartered in Cambridge, Massachusetts, Zumutor has raised $26.2 million in nine years. Its early-stage investors include KITVEN (Karnataka Information Technology Venture Capital Fund), Accel, Aarin Capital, and Chiratae Ventures.

“Once Zumutor establishes the first molecule through the IND stage, it will give an impetus to the next round of funding to generate data on the other molecules in its pipeline,” said an early-stage venture capital investor in Zumutor, requesting anonymity.

The biotech landscape

The global market for therapeutic monoclonal antibodies — a type of protein developed in the laboratory – is expected to generate revenue of $300 billion by 2025, according to a research paper on 'Development of therapeutic antibodies for the treatment of diseases' in the Journal of Biomedical Science.

"The market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential," the paper explained.

Other notable biotech ventures in India include Curadev, Bugworks Research, Immuneel Therapeutics, and Aurigene Discovery Technologies.

Last month, Immuneel Therapeutics announced its Series A fundraising round of $15 million on the back of its Phase II trial in India for Chimeric Antigen Receptor T-cell therapy (CAR-T) for the treatment of blood cancer. The company was founded by Kiran Mazumdar-Shaw, Dr Kush M Parmar, and Dr Siddhartha Mukherjee in 2019.

In February, Bugworks Research raised $18 million in a Series B1 round to support the clinical development of its novel broad spectrum antibacterial agent, as well as the pre-clinical development of its Adenosine immuno-oncology asset.

Aurigene, a wholly owned subsidiary of Dr Reddy's Laboratories that focuses on novel therapeutics for the treatment of cancer and inflammation, has out-licensed several compounds to pharmaceutical and biotech companies for global clinical development.

Zumutor’s path is unique in comparison. “Zumutor is taking the NK-cell approach. There are quite a few players doing the T-cell approach,” said the VC investor quoted earlier. “The NK-cell approach can either complement T-cell immunotherapy, or branch out on as a standalone immunotherapy.”

Treading a different path

Zumutor has three molecules in its development pipeline: ZM008, ZM012, and ZM014.

According to Zumutor, the approach of its lead molecule, ZM008, is to target tumour cell receptors that block NK cell inhibitory signals, and enable NK cell activation to generate a potent immune response. Dr Maloy Ghosh, Chief Scientific Officer of Zumutor, is the architect of this approach.

"From 2016 onwards, we focused all our money on ZM008, and have been taking it forward through all of its data," Kavitha said, referring to the run-up to the pre-IND programme of the US FDA.

Zumutor has consciously chosen a path to get US FDA approvals that call for a variety of the most granular data on the monoclonal antibody. Generating that data requires a number of studies and manufacturing of the product, which is expensive.

The funding ecosystem for this kind of drug discovery, however, is not much evolved in India, said the VC investor in Zumutor. Between 2016 and 2022, the biotech sector has seen a shade over 40 deals grossing $309 million, according to data from Venture Intelligence.

“It has been challenging to raise funds, get investors, and it is all about the data finally. It is a chicken-and-egg situation: unless you have the money, you can’t generate the data. And unless you have the data, you don’t get money in the next round," the investor explained.

Since 2016, Zumutor has also cultivated a research partnership with New Jersey-headquartered Catalent Biologics, which provides biotech companies with development and manufacturing solutions for new biological entities. 

This paved the way to an agreement in early 2020, whereby Catalent would provide process optimisation and drug substance manufacturing services from its site in Madison, Wisconsin. Manufacturing ZM008 would cost Zumutor at least $3.5 million.

At the time, Zumutor was targeting an IND application to the US FDA by the end of 2020. Although this didn’t happen because of the pandemic, the company used the year to generate in vitro (studies performed outside a living organism) data in its Bengaluru lab.

Even as the studies were on, Kavitha sought to raise capital in the second half of 2020, which culminated in a fund-raising round in early 2021, with two new investors Siana Capital and Bharat Innovation Fund.

“We have spent cash and capital like any US company will spend for data generation,” Kavitha said. “This is because all of our data is generated by means of partnerships in the US.”

The platform factor

Finally, there is one more approach where Zumutor is different. Between 2013 and 2015, it built a technology platform called INABLR that would power its antibody identification and optimisation process, as opposed to in-licensing the platform services from a company in the US.

The proprietary antibody discovery platform has three elements to it: a human library, a synthetic library, and a semi-synthetic library. 

“INABLR was designed and executed to ensure that antibodies that were generated were unique, had improved half-life, lower toxicity, better compatibility, stability, and thus improved antibodies,” Kavitha said.

The Zumutor investor said this was a key factor in the funding. “What also attracted us to Zumutor was it was trying out a platform play. For any investor, a platform play makes more sense than a one-off drug discovery project.”

The INABLR platform play brings the possibility of services (and revenue), as well as multiple molecules emerging from it. So far, Zumutor has one commercial engagement with Syngene International, and one academic collaboration with Harvard Medical School around INABLR.

Crucially, INABLR has been the genesis point of the three molecules in the company’s pipeline. So, the patents that get granted will be for INABLR and the monoclonal antibody as it progresses through each clinical trial.

“The platform has a services play also, but that is a double-edged sword: if you get into services, you will get distracted from drug development,” the Zumutor investor said. “Success with the IND stage will give an impetus to the whole thing. The first molecule is always much tougher.”

By Kavitha’s estimate, it takes between $15 million and $20 million to get a first-in-class asset to an IND filing, including clinical manufacturing.

For now, all eyes are on ZM008. By November, Zumutor will know if it is ready for Phase 1 trials.

The biotech space “has traditionally been the preserve of western countries,” the investor said. "We knew this was a long-haul investment, maybe not meant for most institutional funds in India. It was more to see what happens in this space — and whether India can deliver the goods when it comes to drug discovery.”