Dr. Ravi Ananthula on Leaving Dr. Reddy’s to Transform Pharma

Pharma Now: Welcome to Pharma Now, Dr. Ravi Ananthula. I recently went through your bio and I was very impressed. You are the son of a farmer. You moved to Germany to pursue your post-doctorate studies and get an MBA. Today, you’re a Pharmaceutical Development Scientist, building new software. Your journey is very impressive and inspiring. So, let me start from the beginning. You used to live in a remote town outside Hyderabad. What motivated you to set up PharmaDEM and achieve so many accolades?

Dr. Ananthula: First, thank you very much for having me. I'm really happy to share my journey with you. I was born into a middle-class family, and money was never my intention. I always wanted to do something different, something socially impactful. I realized that the life science field impacts humankind. So, I pursued an education in life sciences. I especially focused on medicinal chemistry because that’s where you learn about discovering new medicines. It has the highest impact on humankind.

I completed my PhD in drug discovery, specifically antibacterial drug discovery. When I was pursuing my PhD, many technologies were not available in India. This was back in 2002-2003. At that time, I heard about molecular modeling, which is useful in drug discovery. Being a core chemist, I had never tried this. It was available only in one lab in the Hyderabad Central University. So, to learn, I used to go there every day. I had not registered for a PhD, but I went there and made some friends there just to learn the subject. 

Later, when my PhD was registered, I used technology to integrate it with chemistry. So, we were the first group in 2004-2005 to bring Medicinal Chemistry Drug Discovery into India. Today, after 20 years, most drug discovery scientists in pharma companies are my friends or juniors who learned drug discovery from me and worked with me back in 2004-2005. You can name any drug discovery scientist in any pharma company, and I’m sure they might be my student or colleague or were trained by me.

Pharma Now: That’s a notable feat, Dr. Ananthula. I’m sure having so many connections helped you set up your company. However, before I ask about that, I have an important question: You completed your PhD in India and pursued your PostDoc in Germany. What made you come back to India?

Dr. Ananthula: Actually, I did not pursue my PostDoc immediately after my PhD. I completed my PostDoc out of need. In drug discovery, I realized that we were doing a lot of computational studies and saving a lot of time and resources, but many of my developed medicines were killed once they crossed from the drug discovery stage to the drug development stage, which is the pre-formulation stage area. Pharmaceutical drug development has three stages: drug discovery, pre-formulation, and drug development. In drug discovery, you make an active pharmaceutical ingredient (API), which is the core medicine. In pre-formulation, you maintain the stability of the medicine. In drug development, you convert the API into a tablet, cream, or injection. 

So, I noted that many of the drugs I discovered were getting killed before they reached drug development. Later on, when I was working at Dr Reddy’s Laboratories in drug discovery and drug development, I was designing molecules, and most of them were getting killed in late stages. So, I asked my formulation scientist and preformulation people why they were stopping my drugs. They told me that my drugs had solubility and absorption issues. I thought that there were chances to revamp my drugs, but no rational testing happened. 

Then, in 2010, I realized that there was a lot of scope for rational drug development. However, computational chemistry for drug development was not available in India. This was because no one was doing this type of work, and drug discovery was just established at that time. Then, I identified people in other parts of the world who were using this technology. I talked to someone who was doing preformulation modeling in his lab in Germany. I talked to him quite extensively and decided I wanted to pursue my PostDoc. He accepted my application, and I went to Germany. My career was very good at Dr Reddy’s, but I stopped and I went to pursue my PostDoc.

Pharma Now: That’s certainly a different route, I think most students pursue their PostDoc immediately after their PhD. They never take a break and work in the industry. I think your perspective was different and could be an eye-opener for many students. You did your PostDoc out of need and not because it’s the “correct route”. Is that correct?

Dr. Ananthula: Yes, I pursued a PostDoc because no one could teach me about the technology. There are only two scientists in the world working on computational modeling beyond drug discovery, and I had one of them as my mentor. Later, he became the chief scientist at Pfizer. After 10 years, we founded the International Computational Chemistry Consortium. He became the first chairman and founder of the consortium. He has nominated me as the next chairman of the consortium after his departure in two years. 

In the Consortium, I was responsible for mentoring many computational chemists from the top 20 pharma companies, who worked on a common task. Computational chemists from companies like AstraZeneca, Pfizer, Bristol Myers Squibb, and Amgen were managed by me and made to work on a common task. Through this, we had two important publications: one on solubility and another one on process chemistry. The publications were: The utilization of the computational chemistry for process and drug development needs and the utilization of computational chemistry for Formulation Development. We built models for both, which took 2.5 years. So, you can imagine my position: I had to manage the heads of top companies and ensure they worked on a common task in addition to their original work. I had to keep them motivated and ensure they delivered on the common project for 2.5 years.

Pharma Now: I’m sure that was challenging, but this was probably a huge achievement for you.

Dr. Ananthula: We delivered it successfully, and we published our work. After that, I made one more consortium. I delivered two consortiums in 6 years with complete publications. Managing such a project is not just creating a consortium and conducting some meetings. It was about keeping it aligned for 2.5 years, making them do the real work by writing, publishing, and delivering. I was satisfied with the project.

Pharma Now: That’s truly inspiring, delivering two consortiums is a huge feat. But, all this work was in the drug development area–how did you turn to software?

Dr. Ananthula: That's a very good question. Let me give you a quick background. At Dr Reddy’s–or any other pharma company–if you have to convert a solvent from soluble to screening conventionally, you have to take 10-15 solvents and put your API in them. Then, you visually see and submit the result, all of which happens within 1 week. During this, you have to consume the API, which is costly. In large pharma companies like Eli Lilly, they synthesize only 1-2 grams of API because it is very costly and you don't have the luxury of doing all the tests. But if you are unable to identify good solvents, you have to screen several solvents several times– which is both a time- and material-consuming process. 

So, while screening solvents, my colleagues gave me the structure of the molecule and I had to screen all solvents approved by ICH. Then, I gave them a list of the top 10 solvents they could use. They would test each other and find the right one. Even after my colleagues at Dr. Reddy’s moved on to different companies, they would call and ask the same question. This also happened with my colleagues at Eli Lilly, who went out to other companies and felt that technologies like solid-state screening and polymorph screening were missing. 

When I was working with the International Computational Consortium, we asked ourselves, “What is the most important problem that you have to work on?”. There were many things. To be frank, I had worked on almost all of these problems already in my previous companies and had all models ready. But, I couldn’t give access to them because they were proprietary.

Most of my friends asked me to become a consultant. They requested services like volume of screening, solid-state screening, solubility, and stability prediction. Then, I wondered, “If I am doing this job for one company, how many other companies can I serve simultaneously?” I had built niche technologies. I learned these technologies as I moved from Dr Reddy’s to Germany to Eli Lilly. It took me 11-12 years to build this knowledge and technology. 

During the COVID period, I was scared and wondered, “If something happened to me, what would happen to the things I had invented”? I thought of writing a book but I felt that few people read books now. So, I finally decided to make software and make this technology available to everyone. I made it easy so that people don’t need me for calculations, they can do it on their own at the same level of accuracy and precision. I made it user-friendly with accuracy, and I packed all my knowledge into the software.

Pharma Now: Amazing. Everything you learned, you converted into a code, or should we call it a new subject?

Dr. Ananthula: Yes, it's an evolved subject called Computer Aided Formulation Design (CAFD). I started this subject by incorporating science and expanding.

Pharma Now: Since you launched this software, what accuracy have you achieved? How many projects have you completed?

Dr. Ananthula: In the last four years, we have completed 70+ projects with India’s top 10 pharma companies. We have 85% accuracy. All the Big Pharma like Dr. Reddy’s, Cipla, and Glenmark are our clients, and they are not just one-time clients, they are recurring clients. Today, in our client list, we have many big contract research organizations) (CROs), like Aragen Life Sciences, with more than 5,000 chemists working every day. Many big companies consistently use our software, and they have it in their SOPs as well. They have seen that it is successful. They know that if PharmaDEM claims one formula as stable, but if they find in the lab that the formula is somehow wrong, they won’t question us, rather they will question their analytical team.

Pharma Now: That's because of the success and accuracy rate of your software.

Dr. Ananthula: Yes, because they have seen that the results are consistently correct, and they failed only three times. Two times, the software field with two big companies where. Our software was showing that the formulations would be stable but their analytical team said otherwise. Still, their formulation scientist did not approach us, they directly questioned their analytical team. In reality, there was indeed a mistake from their side.

Pharma Now: Since COVID, many new technologies like artificial intelligence (AI), machine learning (ML), and deep technology have been dominating drug discovery. Of course, many of these technologies are still buzzwords, and a lot of use cases are yet to be developed. But. How are you implementing these new technologies in your software?

Dr. Ananthula: I did not want to implement only AI and ML. AI is an algorithm in which you feed the data and it learns. In ML, you already have a database, and you build a model that is fixed. My model doesn't work on the data, it works on first principles. For example, F = ma, as long as you have mass and acceleration, you can predict the force. It doesn't require hundreds of data files or a huge database. 

There are two kinds of science: fundamental and application science. I focused on application science, where many equations are established and published by several academicians. I focused on utilizing them for the industry’s needs. 

I used the fundamentals of chemistry and physics in AI and ML models, integrated science and technology, and made real applications. Today, solvent screening is done in the lab for 2 months because you have to test all 72 solvents and multiple formulations. Instead, if you use my software, you can do solvent screening in 1 day. In 1 day, you can screen all 72 solvents and identify the top five solvents with the highest possibility. Then, on the next day, you can do solvent testing and submit the solvent and formulation for stability analysis.

Pharma Now: This is extremely beneficial in industrial settings where optimal resource utilization is a must. How much resources and time does the software save?

Dr. Ananthula: A lot. You can save around 40% of resources and 30-35% of the project time. The analytical burden is reduced by 60%. This is the future. I’m sure that one day, people will have to turn to this path.

Pharma Now: A 60% reduction in analytical burden is quite impressive. It makes a huge difference in Big Pharma where timelines are strict. What is the acceptance of your software in the pharma industry?

Dr. Ananthula: Again, this is a very good question. In the pharma industry, people are accepting of digital solutions and advances. However many people invested in or used the wrong products or methodologies. A person from Big Pharma told me, “Dr. Ananthula, we always support digital technologies. We invested 25 lakhs in a company that promised good process modeling. We spent 6-7 months and a lot of money on the project, but the result was painful. After that, we’ve lost faith in digital technologies.” This is a common story among many companies.

Pharma Now: Yes, unpleasant experiences can put you off these projects and developments. But, this certainly means that people are willing to accept change; they’ve just had bad experiences and are now wary.

Dr. Ananthula: There is no problem with people’s mindset. I would say the problem is with identifying the right combination. Model building and digital integration are different from the person implementing them, the tools used, and the expectations set for the client. So if someone can do proper implementation, they will be successful. In the 19 years of my career, I have dealt with very complex projects, projects where there’s no literature. For example, I established the peptide solubility model in 2018. Even today, there is not a single article on how to build a peptide solubility model or predict peptide solubility in organic solvents. I also made a peptide permeation model in 2019. To this date, no study on small molecular permeation modeling has been published, especially on peptide permeation.

Pharma Now: Excellent! Do you now work exclusively in software or are you still working on drug discovery?

Dr. Ananthula: I did drug discovery in my previous companies. If we talk about taking risks, the answer is no. I didn’t take the risk for financial needs because I didn't want to become a multi-dollar company owner. I developed this company only because my subject was limited to one company, and I wanted to expand this subject to all the companies, especially Indian pharma companies. I want to bring all international technologies that I learned in the last 6-7 years, including non-conformance manufacturing technology and drug development technologies, to all pharma companies.

Pharma Now: I think integration of such technologies is a necessity right now. I recently read an interview with Kiran Mazumdar-Shaw. She talked about India’s huge contribution to vaccine and API manufacturing. However, she mentioned that we provide only 2% of the value. We don't have many patents that are commercialized, and our investments are low. What do you think about this?

Dr. Ananthula: I agree. Let me add one more point: If people use the same processes for 10 years, how will they add new value? I read an article by Dr Narayana Murthy, the founder of Infosys. It’s a 30-year-old article in a Telugu newspaper. The article stated “If you can do a task in 8 hours today, tomorrow you should be able to do it in 6 hours. Only then you will have time to learn new things.” I’ve followed this my entire career. I should be able to cut down the time for each task, the only way to cut it down is through technology.

The same applies to the pharma industry, in terms of project timelines and project value. For example, today, you are doing a 100-million-dollar project, but 10 years ago, you were doing the same 100-million-dollar project, and you have a pipeline of 100-200 million dollars for the next 5 years. This is because the human resources and practices you follow are the same as those 10 years ago. You haven’t gathered the courage to take on high-value projects. Why are you not targeting 500-million-dollar projects? Only 3-4 companies in India can take complex and generic projects. The remaining companies are comfortable working on low-hanging projects. 

For example, new chemical entities (NCE) are a next-generation thing because no one is thinking about NCEs in this generation. If you see in the US or Europe, even startup companies are working on NCEs. Before I went to the USA, I always thought, “What is missing? Why are we unable to develop NCEs? Why can’t we make drugs? Don't we have money?” Yes, we have money, and even if you don't, there are hundreds of investors willing to invest in companies. In Europe and the USA, a small startup can generate money. Here, in India, we have Big Pharma! If they wanted to raise funds, they would easily be able to. It's not about money. It’s something different. 

When I went to the USA, I searched for the answer to this question. Even small startups in the USA are doing research in drug discovery and NCEs, but India's Big Pharma with 20-30 years of experience is not picking up these projects. I realized that it’s the thought process in Europe and the USA. They're directly working on NCE projects, and they have one thought on their minds: they want to work only on NC projects. There is no safe zone. They aim to hit the big goal. After that, they will raise funds. They can raise funds, and this is not about money, it's their ability to raise funds. India has money as well, and we hardly need 7,000 crores to make medicine. Considering India’s GDP, it's not that we don't have money. So, it's not about money, it's more about technology, which is a big gap and that technology is what I want to bring to India.

Pharma Now: While I’m no expert in the field, I can say that you’ve succeeded to some extent in bringing new technologies to India. Best wishes to you, Dr. Ananthula, as you bring more new tech to India. I'm sure with this passion, you will achieve this feat. It was wonderful talking to you. Thank you for joining us at Pharma Now.