COVID-19 vaccine: Top 5 Indian biotech firms developing antigens for the world

Your COVID-19 vaccine could come from one of these Indian biotech giants

Highlights

• At least eight COVID-19 vaccines are being developed in India.
• One company, Biocon Ltd, is preparing two candidate vaccines through its R&D arm and partnerships with US firms.
• Serum, working with Oxford University, is a front-runner in the global vaccine race.
• Scientists in numerous Indian biotech firms are working feverishly to ramp up COVID-19 vaccine tests.

Dubai: India’s free-wheeling media often flippantly tell stories about some weirdos prescribing cow-pee-cow-dung, or even corrosive chemicals, as some kind of cure-all for everything from cancer to COVID-19.

This masks the fact that India's researchers are at the forefront of biotech. There are at least eight potential COVID-19 candidate vaccines in the works by its underrated biotech sector.

Take this: There are over 600 companies and 2,800 startups in the subcontinent’s biotechnology scene.

That means intense competition fueled by an abundance of a critical mass of local talent. Today, India has produced the planet’s biggest manufacturers of flu and hepatitis vaccines, prophylactics, insulin, generics and “bio-similars” (copy versions of biologic drugs).

These companies, a number of them listed on Bombay Stock Exchange, generate billions of dollars. The sector contributed $12 billion to India’s economy, in 2017, based on latest industry data available.

Biotech powerhouse

The subcontinent has emerged as a biotech powerhouse. With the COVID-19 threat — having infected more than 5.4 million people worldwide and killed over 345,000 — home-grown companies are out to salve the world’s clamour for a safe, effective and affordable vaccine.

WHAT IS A VACCINE?
Vaccine is a biologics used to boost a person's immune system and provide immunity against pathogens. The solution consists of either a weakened (attenuated) or “killed” form of disease-causing microorganisms that enhance the immunity without causing diseases.

Nature listed 115 COVID-19 candidate vaccines last month, with about a dozen already in advanced stages of human trials. 

This heightened R&D marks a scientific marathon involving the world’s best minds to combat a clear and present danger. Here’s the list of the top Indian biotech firms, and why they’re the front-runners in the global dash for a coronavirus vaccine:

1. Biocon Ltd.

Biocon Ltd, based in Bangalore, is India’s vertically integrated biotech powerhouse. The company, listed on BSE Sensex, started producing plant enzymes in the garage of a rented house in 1978 with a Rs10,000 capital saved by its founder, Kiran Mazumdar-Shaw.

The company, which had an IPO in March 2004, emerged as one of India’s top bio-pharma firms, employing about 5,000 people today.

Now, it is the world’s biggest producer of insulin, injectable hormones that help control blood sugar in diabetics.

Biocon operates in Malaysia, Singapore, the UAE, Europe, US. In its home lab, it employs hundreds of top-class biochemists.

Mazumdar-Shaw, who studied zoology and trained as a brewer, is one of India’s top home-grown businesswomen, and has taken on the challenge of beating COVID-19, through her company’s R&D arm, SynGene.

Biocon’s work on COVID-19

The company is developing a novel customised non-replicating measles virus-based vaccine, an antigen therapy that can be commercialised quickly. Biocon is also developing two new generation “repurposed” technology for treatment and an antibody diagnostic kit.

Mazumdar-Shaw seeks to deliver the COVID-19 antigen into the human body to develop immunity against the virus through a virosome platform.

Biocon is working now with Pune-based biotech firm Seagull Biosolutions on a novel active virosome (non-replicating artificially-created virus) vaccine project. “We are helping them progress the development. It can reach human trials in another six months," Mazumdar-Shaw, told Indian media.

Dr Vishwas Joshi, founder and director of Seagull, explained the technology for producing this vaccine uses, for the first time, customised non-replicating measles virus vector platform.

This is done by transplanting target antigens into measles virus to develop the vaccine, which can then trigger the growth of antibodies in humans to fight the coronavirus.

Seagull, founded in 2011 (funded by India's Department of Biotechnology, ICICI and Gates Foundation) developed the technology five years ago, and demonstrated in animal models for potential vaccines against chikungunya, ebola and dengue.

Biocon’s R&D arm Syngene had been been working with Seagull for the last 18 months, and are now taking the COVID-19 vaccine project forward,

Mazumdar-Shaw said Biocon is also working with a number of American companies to develop antibody injections or therapies that be an antidote to coronavirus.

BIOLOGICS
A biologic drug (biologics) is a product that is produced from living organisms or contain components of living organisms. Biologic drugs include a wide variety of products derived from human, animal, or microorganisms through the use of biotechnology.

Faster trials

"Human trials may start by July. The Phase I and pivotal Phase II can be done much faster and it can be developed like a vaccine,” she added that the vaccine can be commercialised in nine months to one year.

Antibody treatment promises to help cure infected patients and can be used as a prophylactic (protective agent) for high-risk people.

Mazumdar-Shaw said Biocon is trying two of its unique drugs or therapies as a treatment in COVID-19.

The first is 'CytoSorb', a novel blood purification therapy done through dialysis. The drug is indicated for Sepsis to reduce excessive levels of inflammation causing agents in the blood. By purifying the blood using this therapy, potentially deadly systemic inflammatory response syndrome (SIRS), a major cause of death in many COVID-19 patients, can be reduced.

Another therapy Biocon is attempting is reusing 'Itolizumab', the world's first novel anti-CD6 antibody developed by Biocon to treat psoriasis. The drug is also found effective in treatment of other autoimmune diseases like rheumatoid arthritis, psoriatic arthritis and multiple sclerosis.

BIOSIMILARS
A biosimilar is a biologic medical product highly similar to another already approved biological medicine. Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines.

2. Bharat Biotech

Set up by Krishna Ella, Hyderabad-based Bharat Biotech International Limited (BBIL) has 50 global patents to its name, of which five are for new molecules.

In 2016, the global private equity company Carlyle Group announced a minority stake in Bharat Biotech from existing investors ICICI Venture, International Finance Corp., and Subhkam Ventures.

Recently, the Indian Council of Medical Research (ICMR) has partnered with Bharat Biotech to develop a fully indigenous vaccine for COVID-19, the health research body stated on May 9, 2020.

The vaccine will be developed using the virus strain isolated at the ICMR's National Institute of Virology (NIV), Pune, a company statement said.

The strain has been successfully transferred from NIV to BBIL, it added. "Work on vaccine development has been initiated between the two partners. The ICMR-NIV will provide continuous support to BBIL for vaccine development. ICMR and BBIL will seek fast-track approvals to expedite vaccine development, subsequent animal studies and clinical evaluation of the candidate vaccine," the health research body said in the statement.

Partnership with Thomas Jefferson University

On May 20, Bharat Biotech also announced that it has entered into an exclusive agreement to develop a COVID-19 vaccine candidate created at Thomas Jefferson University in Philadelphia, US.

The vaccine candidate, developed in January by a team led by infectious diseases expert Prof Matthias Schnell, uses an existing “deactivated” rabies virus as a vehicle for coronavirus proteins. This approach, using a vehicle or "carrier" vaccine, is known to generate a strong immune response, and is authorised for the whole population, including children and pregnant women.

Preliminary tests on animal models show the vaccine triggered strong antibody response in mice. Currently, researchers are evaluating if vaccinated animals are protected from COVID-19 infection and results are expected in June.

3. Serum Institute of India

The Serum Institute of India (SII) Pvt. Ltd., based in Pune, is the most advanced among India’s top pharmaceutical companies in terms of vaccine research and production.

A leader in MMR (measles, mumps, rubella) and hepatitis B vaccines in India, Serum is known for coming up with vaccine products in the country at affordable rates.

In 2007, Serum unveiled its indigenously manufactured low-cost Haemophilus influenza type b (Hib) conjugate vaccine under the brand name of HibPRO in India for Rs375 ($8) for a single dose vial.

A vaccine supplier of UNICEF, Serum has recently partnered with Oxford University’s Jenner Institute which began trials of the “ChAdOx1 nCoV-19” candidate vaccine in humans.

SII recently unveiled plans to produce up to 60 million doses of ChAdOx1 even if it still under clinical trial in Britain. ChAdOx1 is considered a leader in the global race to develop an antidote to the novel coronavirus.

It’s a bold risk-taking move.

But one that could pay off if Phases 2-and-3 trials of the Oxford vaccine prove both safe and effective.

By volume, Serum is already the world’s largest maker of vaccines. It is set to mass-produce ChAdOx1, in a deal with Oxford, after entering Phase-3 of human trials.

Though “ChAdOx1 nCoV-19”, is yet to get past Phase-3, Serum decided to start making it after it had shown pre-clinical promise and had progressed into human trials, Serum Chief Executive Adar Poonawalla said.

He said: “I can take a little risk and sideline some of the other commercial products and projects that I had planned in my existing facility.”

The Oxford vaccine trials are due to finish in about September.

Serum plans to make the vaccine at its two manufacturing plants in the western city of Pune, aiming to produce up to 400 million doses next year if all goes well.

Serum’s Poonawala said they may price ChAdOx1 Rs1,000 ($13.20) per shot, though governments would give it to people without charge.

Over next five months, Serum will around 3-5 million doses per month.

Codagenix, Themis partnerships

Serum has also partnered with the US biotech firm Codagenix and Austria’s Themis on two other COVID-19 vaccine candidates and plans to announce a fourth alliance.

On April 30, 2020, Oxford stated that it’s also partnering with AstraZeneca to manufacture and distribute ChAdOx1 as quickly as possible.

It said the vaccine will be made available on a “not for profit basis for the duration of the coronavirus pandemic”.

4. Cadila Pharmaceuticals-Novavax

In partnership with India’s Cadila Pharmaceuticals, the US-based Novavax is using the virus-like particles (VLP) platform, which has been previously used for the papilloma virus vaccine.

The trial uses Novavax’s platform, a pre-fusion protein coronavirus platform made using its proprietary nano-particle technology, called Matrix-M.

This vaccine is also undergoing Phase-I trial in the US and Australia.

Novavax Inc. was among the first ones to announce it was working on a candidate too. Novavax uses an adjuvant (a substance co-injected with an antigen) to enhance immune responses and stimulate high levels of neutralizing antibodies against SARS-CoV-2. It stimulates the entry of antigen-presenting cells into the injection site and enhances antigen presentation in local lymph nodes, boosting immune response and helping an immunized person make antibodies against the virus.

Novavax has also has marketed seasonal influenza, H1N1 and rabies vaccines in India.

The partnership goes back to 2017, when Cadila and Novavax completed construction of their joint venture vaccine manufacturing plant in Dholka, India. Cadila holds 80% stake in the joint venture, the remaining 20% will be held by Novavax.

5. Shantha Biotechnics

Shantha Biotech has manufactured the world’s first effective oral cholera vaccine. The vaccine, called Shanchol offers one distinct advantage: it is poured directly into the mouth and does not need any extra water. It is proven effective, with doses given two weeks apart.

The vaccine has not been used in India because cholera outbreaks are rare, but it is used all over the world in emergency situations, including in Haiti and Myanmar.

Shantha shook the market in India when it rolled out its recombinant hepatitis B vaccine at 1/10th the price of the imported vaccine.

It has also received WHO pre-qualification for its combination vaccine of DPT and hepatitis B, Shantetra, enabling supplies to the UN agencies.

Shantha targets infectious diseases and oncology as its primary areas of interest for conducting R&D activities.

It also collaborates with research organizations such as the CCMB and the Indian Institute of Science. It also had a research tie-up with South Korea’s International Vaccine Institute, for the development and transfer of technology for various vaccines.

Contract research is undertaken at Shantha’s 50,000 square feet R&D center. Contract research work are in the areas of gene cloning, monoclonal antibody development, expression and purification of recombinant proteins by fermentation and purification process optimization, development of polyclonal antibodies, and development of analytical methods.

TAKEAWAYS

• The knock-on effect of the pandemic is haemorrhaging the world economy, precipitating an R&D race — as well collaboration among top scientists dealing with biologics.
• With COVID-19 vaccines trials, the world is not starting from scratch. An early vaccine for SARS-CoV-2 is entirely within the realm of possibilities.
• The world’s top biotech firms have had some experience with coronavirus vaccines against SARS-CoV-1) and the MERS.).
• It’s possible several vaccines using different technologies may work, paving the way for large-scale production and competitive pricing.
• Following the rigorous trials, mass producing the vaccine is the next challenge. This is where Indian biotech firms could play a key role, via large-scale production and competitive pricing; they could hold the key to easing lockdowns the world has come to know.
• Should any one of these candidates pass the test and ramp up production soon, it’s possible the fear and stigma associated with the pandemic may wear off.
• This competition should be managed well, in the sense that trials are done properly and the flow of supplies of raw materials is ensured.
• This virus may be deadly and highly transmissible. But there are two things it doesn’t have: common sense and the ability to work together. When people work together, great odds can be overcome.