Kochi-based PNB Vesper’s semi-virtual web of researchers, universities, and CROs across continents has some promising leads in the pre-clinical pipeline. Promoter PN Balaram says this cost-effective research model is the way forward to achieve India’s drug research goals
Usha Sharma & Sanjiv Das
Most promoters of pharmaceutical companies in India have traditionally focussed more on manufacturing generic drugs. But a Kochi-based entrepreneur decided to harness the research of scientists from across the world, and create a business model that thrives on R&D. PNB Vesper is ‘a semi-virtual’ mode, with most of its preclinical research and development activities being conducted by academic and commercial organisations in the UK, the US, Thailand and India. Though the business is in its early days, it’s interesting to note its developments and growth vision.
PN Balaram, Managing Director of the company started his entrepreneurial journey when he was 20 years in a collaboration with Japan’s Toshiba to manufacture televisions. While he established his business in the electronics and DTH satellite marketing sector, he also established businesses in the distilleries and foods sector. He then ventured into the research domain with the launch of Cybele Herbal Laboratories.
So what motivated Balaram to venture into the research-driven pharma industry, especially with no background in this domain? Balaram says, “I cannot give a definite answer for this question. Circumstances led me to conduct drug research. Maybe the almighty assigned this task to me. One thing is for sure, if we are successful in our research, the society will be majorly benefited.”
The journey so far
As American writer Irving Stone says, “To become a master at any skill, it takes the total effort of your heart, mind, and soul working together in tandem.” So, how did it all start for PNB Vesper? Balaram launched Cybele Herbal Laboratories to manufacture scientifically-proven herbal medicines mainly for the international markets. Revealing more, he says, “We were the first ayurveda company to set up a WHO-GMP facility in Thodupuzha , Idukki District in Kerala with TGA (Australia) approval. Our scientific approach to herbal medicines along with my passion to do something unique and innovative led to venturing into NCE research.”
During the launch of Cybele Herbal Laboratories, Balaram gauged the market requirements and updated it accordingly. “We started our basic research activities in 2004 and launched PNB Vesper Life Science in 2011. Manufacturing a drug is a roller coaster journey, calling for day-to-day crisis management. With good team work and by God’s grace, the manufacturing process has improved. Today, we are working on six molecules and targeting 10 serious medical conditions. We aim to complete clinical trials of PNB 001 and PNB 028 soon. All other molecules are at different stages of studies. This is just the start of a future major pharma company with in-house facilities,” comments Balaram.
Setting a benchmark
Balaram’s commitment to quality made him set up a WHO-GMP facility in India with TGA-Australia approval with an investment of Rs 18 crores in the manufacturing of NCEs. As per the information in the public domain, the standard cost to develop a new drug is around $2 to $2.5 billion (more than Rs 15000 crores). Drug research is a risky business and the success rate is minimal. This is the reason why even big companies are reluctant to invest in NCE research. Hiring the right drug research professionals for a company based out of India is also difficult. Yet, Balaram seems unfazed by these obstacles and is optimistic about the risk he has taken on. Balaram reasons that, “Even though some big Indian pharma companies entered into the drug research arena, the success rate is almost nil or very low. We have taken this as a challenge and want to show the world that India is equally capable of developing new molecules for serious diseases. Our key objective is to provide remedies for unmet medical diseases at affordable rates. We also want to highlight our innovative research model to the world.”
Cancer-driven research activities
The rising incidence of cancer drew the promoter’s attention. Giving details about the company’s focus areas for research, Balaram says, “A majority of our research work is for cancer indications. In addition to higher efficacy (in treating cancer), our molecules have a range of extra clinical benefits such as reducing depression, anxiety as well as pain. We are showing a new cost-effective research model to the world involving the best universities, CROs and scientific talents in our research laboratories. We have developed six molecules for 10 serious diseases. And two of our molecules are already in the different clinical trials as well. Since all our molecules are targeted therapies, we expect maximum efficacy, longer life span and less toxicity in patients. This is our key objective for our research which provides maximum benefits to the patients at an affordable cost.”
Explaining further, Balaram mentions, “We are trying to develop targeted therapies for cancer treatment with no side effects or fewer side effects. They are all allied around neuropeptide targets of the gut – brain axis. Our focus is to use key peptides, which control physiology and various pathways in the human body. These depending on the disease, are either modulated or switched off completely by our molecules. One of our research targets is called cholecystokinin receptor. It is the target organ is the pancreas and we target selectively and irreversibly an isoform of the cholecystokinin receptor, the CCK-C receptor.”
Revealing more about the company’s cancer and pain management research, Balaram informs, “One of our major targets is cholecystokinin (CCK). It was originally discovered as pancreocymin, a peptide to stimulate the pancreas to release pancreatic enzymes. Different receptor subtypes are present CCK A, CCK B equivalent to the gastrin receptor and mutation of the native CCK receptor leads to the CCKC receptor isoform, which is the target of our drug cancer molecule PNB-028, to put it in a nutshell. PNB-001 targets the CCK B – gastrin receptor and PNB-081 is a CCK A antagonist.”
The five molecules which are in different stages of completion under clinical trial are PNB-001, PNB-028, PNB-081, PNB-101, PNB-291 for inflammatory pain IBD dysmenorrhea, pancreatic cancer, colon cancer, opiate potentiation / opiate tolerance pancreatitis, gastric cancer, lung cancer, small cell lung cancer only and brain cancer, lung / liver cancer respectively.
Commenting on the clinical trial procedures for CCK programme and its effectiveness, he informed “Cholecystokinin antagonist proglumide is marketed under the name Milid, which was available to treat GI ulcers. Devazepide, a CCK A antagonist, which worked clinically in a phase II study in opiate management, paved the way for our PNB-081 as a proof of concept. We develop the first CCK C selective therapy for cancer, PNB-028, and the first CCK B selective therapeutic for inflammation, PNB-001, as a drug to treat IBD and period pain on its own.”
Updating about the clinical trial procedures for its lead molecules, Balaram says, “We have received the Indian FDA approval for our trials and will launch it in India first. All experimental studies were carried out in collaboration with leading institutions worldwide and additionally by outsourcing more standard and regulatory activities to excellent selected CRO organisations like Lambda Clinical Research. We have a precise map of competent and efficient pre-clinical CRO, manufacturing facilities and clinical CROs in India and globally. Later, these drugs will be available for the rest of the world including the US, which is a large market. The profits will be reinvested in India to grow PNB Vesper as a major pharma company.”
Additionally he says, “ Our target areas are pancreatic, colon and stomach initially and if you take these three together, they have a combined incidence of >100 per 100000. If we give a 90 per cent discount on standard targeted therapy costs, we treat 1 million patients only in India. It will result in about $10 billion revenue calculated for a percentage market share. All these diseases are related to food intake, which also increases the risk of type 2 diabetes. For front runner PNB-001, the Inflammatory bowel disease (IBD) market in India is larger than the cancer market and the growths rate of IBD is growing faster in India than in any other country.”
Aid from BIRAC
PNB Vesper has received grants from the US patent ( US patent no: 8,921,577 B2 and Date of Patent: Dec. 30, 2014) for its research molecules and financial grants by the Biotechnology Industry Research Assistance Council (BIRAC). BIRAC has also supported the clinical development of novel CCK receptor antagonists for the treatment of inflammatory pain. BIRAC sanctioned Rs 3 crores for PNB001 studies and released Rs 1.5 crore to cover part of toxicity and clinical studies.
“For PNB 028, our colon and pancreatic cancer molecule, BIRAC has shown interest to associate with us in clinical trials. We are waiting for the final sanction order from BIRAC and have requested to speed up the process,” he says.
Balaram seeks further assistance from BIRAC in the form of fund allotment for its high-end research molecule PNB 028. Considering the importance of the molecule, he hopes that BIRAC will assist in the research which will eventually benefit the nation.
Big tickets on the way
The company’s key molecules are in different phases of completion and clinical trial time have been allotted for PNB-001, phase 1and 2a, which will be conducted at a suitable CRO. Phase II will continue directly thereafter. It will ensure that by 2020, PNB Vesper aims to complete PNB 001 phase 2a clinical trial. If everything goes off well, PNB 001 will be ready for launch in 2022.
“Another lead PNB-028 also received IND approval and clinical trial activities have begun for colon and pancreatic cancers. Says Balaram, “We expect to complete the phase 2a trials within 12 months. We are planning to offload a per centage of ownership in each molecule to fund future studies,” informs Balaram. “We have not started any commercial discussion with companies who have shown interest. We are seeking an investment l in the PNB VESPER Molecules, not in the company. ”
Commenting on the patent part, he mentions, “The primary patent application was done in India and patents are granted worldwide, including the US, the EU and all ASEAN counties. A further patent, user patent, will be filed for second-line protection and these endeavours are in due course.”
Going forward, the company aims to launch the lead molecules not only in the Indian market but also in developed markets like the US and Europe. He says, “In future, we will associate with some pharma group, who will have a similar ideology like us. Considering the technical excellence of our molecules, we are sure to tie-up with a good group in the future. With our new management team, we are confident to develop all six molecules currently in the pipeline.”
According to Balaram, PNB-081 is tailored for the US market which is under an opioid epidemic. He plans to launch it in the US market first. This in turn will help to generate more funds to conduct research activities for the rest of the molecules within their pipeline in India. The company aims to launch these products globally in line with regulatory norms.
Apart from this, PNB Vesper has taken some strategic decisions for growth. The company has recently appointed
Dr Eric Lattman as VP Research. He has been instrumental in designing, discovering and developing novel CCK antagonists as analgesics. Balaram says, “The company has an established management team which is headed by Dr Lattman. A highly-efficient development team catapulted PNB-001 and PNB-028 through regulatory hurdles at a high speed and under the most efficient supervision of all CROs involved.” A team of advisers, operating worldwide, are consultants and not employed by the company. Right from research to the formulation, 90 per cent of the work is outsourced. Industry experts work both on a part-time and full-time basis. Some employees have agreed to get remuneration paid post the molecules are launched.
In future, only time will tell whether the success of PNB Vesper and Balaram’s endeavour will help the company gain new heights.