Lab Rats series: Unlocking the kidney for therapy with Helex

Mumbai: In 2009, three graduate students shared a flat in London while studying at King’s College. While Poulami Chaudhuri and Anirudh Nishtala pursued master’s degrees in molecular sciences, Rohini Kalvakuntla studied international management. Over a decade later, the three came together to set up a biotech startup in their hometown, Hyderabad, with a clear and ambitious vision—to unlock the kidney cell for therapy and make it affordable for India.

Getting the right drug into a kidney cell at the right dose without causing toxicity is a massive medical challenge. Helex Inc. is developing first-in-class genetic medicines to target the kidney.

“The motivation was to have top-class medicine and science, but it has to be accessible and affordable for patients in India and worldwide,” said Kalvakuntla, who is chief business officer at Helex.

The idea stems from a large number of innovative therapies—especially for genetic, rare and critical illnesses—remaining unaffordable to the majority of the domestic population, even when launched in India. The seed for setting up an Indian innovation firm was already there, and the idea was further solidified when they came across an article outlining an NGO’s crowdfunding efforts for spinal muscular atrophy—a rare genetic disorder—for children. New-age innovative therapies for this disorder can cost lakhs and even crores for a single dose.

They have filed four patents and have presented their scientific research posters at various global symposiums.

“The three of us have spent a significant amount of time in the West, and we saw what advanced therapies could really do—the promise of it. The idea was to grow that sort of innovation in India,” said Chaudhuri, Helex’s chief executive officer.

Helex’s motivation underscores what several homegrown biotechs aim to do: make globally competitive drugs but keep them affordable for economies like India. They must, however, contend with smaller budgets and a sparse and fledgling innovation ecosystem.

Helex believes their edge comes from the expertise each founder brings to the table—Chaudhuri’s scientific research on genomic medicine, Kalvakuntla’s work in global healthcare consulting, and Nishtala’s experience scaling pharmaceutical operations from the ground up.

The science

Their lead molecule is a single-shot, or single-dose, gene-editing drug for autosomal dominant polycystic kidney disease (ADPKD), a genetic disorder that causes fluid-filled sacs (cysts) to grow in the kidneys, reducing their ability to function over time.

Helex has developed a first-in-class drug delivery system, a technology to deliver specific drugs to specific organs. In this case, in-house-developed lipid nanoparticles (LNPs) encapsulate the drug and deliver it to the target cell in the kidney.

The drug is expected to reach and ‘edit’ the faulty genome to potentially stop or reverse the disease progression in a single shot.

"While gene editing has been validated in patients for other indications such as liver diseases, no therapy has yet been able to reach the kidney. The biggest challenge is delivering therapeutic agents to the kidney safely and in a targeted way, and that is exactly what our proprietary delivery technology is built to solve,” said Chaudhuri.

One of the key therapies used currently, Tolvaptan (a small molecule), slows down cyst growth, but comes with risks like liver injury. The drug’s estimated annual sales, however, were roughly $1.4 billion for innovator Otsuka, and are expected to fetch $200 million annually for generic firms like Lupin.

However, innovations for ADPKD are shifting towards addressing the disease’s genetic drivers.

The challenge

While its science is promising, Helex must establish a ‘proof-of-concept’—an early-stage trial to demonstrate that its therapy can work as intended. “The ADPKD target (gene-editing molecule) we are going after has already been clinically validated through another mechanism, but that approach requires repeat dosing. We are developing a single dose therapy against this clinically validated target,” said Chaudhuri.

“In any new drug development, reaching phase 1 trials, which is essentially demonstrating the drug’s safety in humans, is a key milestone… Even though phase 1 tests for safety, toxicity and profiling, in drug development, safety is always more important than efficacy,” Dr Ratnesh Jain, founder of the Mumbai Biocluster, an innovation ecosystem incubated at the Institute of Chemical Technology in Mumbai, said.

Helex’s lead candidate has not yet entered the clinic; however, they have demonstrated that their lipid nanoparticles can safely enter target cells in mice, other rodents and non-human primates. “Not only deliver, but they can also edit the target cell,” said Nishtala, the chief operating officer.

The next step is to advance the programme towards an investigational new drug application (IND) with the US Food and Drug Administration, which would then enable clinical trials.

Scaling up

This month, Helex moved to a larger lab in Hyderabad’s Genome Valley, from its space at the research institute ASPIRE-BioNEST. “We’ve designed that facility in a way that it caters to all our R&D (research and development) needs but also has enough Schedule M requirements to be able to do other research work,” said Nishtala.

Schedule M, a regulatory framework under the Indian Drugs and Cosmetics Rules, 1945, outlines the mandatory good manufacturing practices and facility standards for drug manufacturing units, to ensure quality aligns with global standards.

The firm has raised $6.2 million in pre-seed and seed rounds, and is now gearing up to raise a Series A round to fund its phase 1 trials. Helex’s $3.5 million seed round was led by pi Ventures. Others participating in the round were Bluehill Capital, SOSV and a global syndicate of investors. However, Kalvakuntla says the company has found ways to increase its capital efficiency by operating as a hybrid company, based partly in US and partly in India, leveraging US expertise while remaining cost-efficient.

It is also pursuing partnerships beyond ADPKD to generate additional revenue and sustain operations. “There are multiple diseases we can tackle within the kidneys, so we are actually looking at partnerships for those, where we can license our technology and co-develop, which will also bring in revenue,” said Kalvakuntla.

Novel drugs are expensive due to the time and cost of R&D involved. How can they make it affordable? Developing in India significantly reduces costs. Secondly, the firm plans to retain commercial rights in India, thereby maintaining full control over how the drug will be priced—while pursuing licensing deals with larger firms for developed markets.

This is the fourth in a six-part Mint series on biotech startups.