Incando Therapeutics – Setting up an early-stage therapeutics company
Incando Therapeutics is an early-stage therapeutics company developing light-based therapies for hard-to-treat cancers, specifically glioblastomas and variants of the disease. The company’s proprietary technology, with development roots at Stanford University and the National University of Singapore (NUS), uses wireless technology to control implantable light devices to dispense on-demand phototherapy directly to tumours. Founded in 2019, Incando Therapeutics successfully raised its seed round in 2020, and is currently working to refine their product and develop treatment procedures for clinical testing. We spoke to Dr Percy Luu, Founder and CEO at Incando Therapeutics, to find out about his experience starting and growing a very early-stage start-up company in Singapore.
Dr Percy Luu, Founder and CEO
BCS: What is the story behind Incando Therapeutics? How was it founded?
Percy: I came up with the idea that became Incando Therapeutics, while working in the Department of Surgery at the Yong Loo Lin School of Medicine, National University of Singapore (NUS) where I was responsible for leading translation for research out of the medical school. As such, I interacted deeply with both the scientific and clinical communities to become familiar with the newest technology and the most pressing medical needs. The goal was to find ways to connect the two to build products and businesses.
One of the technologies that stood out was developed by A/Prof John Ho, a colleague from Stanford University and now faculty at NUS ECE. He was working on implantable photonic devices for wireless light delivery into living systems. One of the key applications was to use an implant to activate light-sensitive drugs to treat cancer. This is a known cancer treatment called Photodynamic Therapy (PDT); however it had never been demonstrated using an implant. The application of this technology towards human cancers held promise and in collaboration with NUS and National University Hospital (NUH) neurosurgery, led by Prof Yeo Tseng Tsai, we chose the aggressive brain cancer glioblastoma (GBM) as our first clinical target.
I worked to build a business case and resources around wireless photodynamic therapy devices for GBM and in March 2019, I left NUS to work full time on the company. After building a team and establishing key resources, we successfully raised our seed funding and became operational at the end of 2020.
BCS: Could you share more about Incando Therapeutics’ technology and its applications?
Percy: Our mission is to enable the use of phototherapy, or light-based techniques to treat human disease. These tools are well established in the world of biology research (especially neuroscience) but have seen limited applications in the clinic. Although we can control light very precisely, its delivery to areas of disease in the body is limited by size and power constraints. Incando is developing miniaturized implantable lights that can be positioned deep inside a patient and can be controlled on demand using wireless technology. It seems quite simple but being able to turn on a light bulb precisely at the site of disease in a patient is tremendously powerful. This is where light-based techniques and light sensitive drugs complete the picture. Local activation of such techniques or drug effects can result in very precise medical effects. This enhances effectiveness, potency, and safety. In grave diseases such as cancer, such precision can make all the difference in patient survival.
Incando’s work consists of two major phototherapy aspects. First, through cutting edge engineering, we aim to make implants that can deliver light anywhere in the body. Second, our biosciences work focuses on optimizing and adapting light-based techniques to benefit patient outcome using research models of disease. Right now, we are focused on intracranial devices and photodynamic therapy for our brain cancer program, but we intend to expand out to other disease targets in the future. For instance, we also have an active neurodegeneration program that uses another light-based technique.
BCS: How would you compare your technology with the current gold standard being used? Can your technology be used for other cancers?
Percy: Glioblastoma is an aggressive brain cancer with a poor prognosis and very limited treatment options. Patients typically do not survive for more than 15 months after diagnosis and treatment. The standard of care treatment consists of surgery followed by chemoradiation therapy. The delicate and complex nature of the brain limits the number of radiation treatments possible. Additionally, currently used chemotherapies fare poorly or develop resistance. This paints a very bleak picture. Unlike other cancers, all of the treatment options for GBM are used up in the first line of defence- and then the cancer comes back. GBM has a depressingly high recurrence rate >90% within 12 months of treatment. There are currently at least a dozen ongoing clinical trials for glioblastoma, consisting of new chemotherapies, biologics or variations of current regimens. Historically, many such trials have failed, and this has been very frustrating.
Our implantable photodynamic therapy system, DeepLight, offers a safe and repeatable option to cancer physicians. In GBM PDT, the patient takes a light sensitive drug that is targeted to tumour cells. This drug is completely safe and inert until activated by the DeepLight device, whereupon it rapidly triggers tumour cell destruction. PDT is not only safe but precise, only affecting cancer cells and sparing neighbouring healthy brain. Significantly, DeepLight can then be used again and over a greater period of time than chemo or radiation therapy, offering a true long-term option for tumour control.
A great advantage and opportunity exists with PDT because it works through a mechanism that is generalizable between cancers. Unlike drug, biologic or cell-based therapies, there is a lower molecular specificity, meaning that this technique can be applied to numerous other cancers. Since the drugs only act where there is light activation, target specificity is further guaranteed. We are actively exploring intractable cancers that may be suitable for DeepLight.
DeepLight device activated by wireless power
BCS: What is the product development stage of Incando Therapeutics and what would be your projected timeline for your product to reach the market?
Percy: Currently we are in the preclinical stage of development. We have completed our proof-of-concept studies and are in the process of conducting the translational research work necessary to move our product towards clinical testing. Our device engineers are working with clinicians to optimize our device usability and to incorporate our procedures seamlessly into the standard medical treatment for GBM. The next stage would be safety and manufacturing where we ensure that the devices are suitable for long term implantation and usage in the body.
As for when we would hit the market, well- medical therapeutics development is a long road. Inclusive of clinical trials, pharma products would typically require between 8-12 years of development time. Purely device-based products require slightly less time, with a lifespan of 5-8 years. According to the FDA our DeepLight therapy is a combination of a device and a drug so, fortunately, it inherits some advantages in a shorter device-based timeline.
BCS: Having secured seed funding, how have you been utilising the funds?
Percy: We proposed a very aggressive schedule with our budget- to reach clinical stage with a human ready product within 2-3 years so we had to work quickly and efficiently. Initially we focussed on building our team, getting our infrastructure together, developing our internal processes, and settling legal and accounting matters. Our industry is extremely regulated so everything has to be above board and compliant- all the way down to the little details of company processes. I also established a small functional laboratory based in NUS. In the first year we quickly established an animal model for brain cancer have been building evidence showing the efficacy and critical parameters of our DeepLight therapy. We put significant resources into engineering, defining specifications and user needs around both our research and clinical prototypes ahead of deep product development. All of this work has continued and converged in 2022, with the end goal of approval for a First in Human (FIH) clinical trial right here in Singapore with our colleagues in the National University Health System (NUHS).
DeepLight device with size reference
BCS: With Incando Therapeutics being a biotech/medtech company, how did you manage to build partnerships and incentivise clinicians to work with you?
Percy: I try to build partnerships with clinicians by building a scientific relationship with them. I come to the table with 25+ years of academic and industry research and a strong neuroscience background, which allows me to connect very quickly. When I speak to doctors, I describe my product and vision in detail, and see how they react to it. This typically results in an active scientific discussion and builds rapport, which usually gets me a second meeting. As part of the active discussions, I fully embrace their input and criticism, as it prevents me from making mistakes in the future. In a second meeting, I will share my progress, and it gets them excited. They get caught up in it, and the next thing you know, I have a partner. Clinician concerns are very important and distinct from those of a scientist, even working on the same problem. I try to work towards an open exchange of ideas in our relationships- this is difficult, but the synergy is worth it.
Many of our clinician partners have deepened their involvement in our work because of the promise of our cancer product. We have kept the pace of research and product development very high so that there is a very real sense that we are making progress with each meeting. Our partners respond to that.
BCS: How did you assemble your team? How do you keep your team engaged in your company?
Percy: Once I had the basic vision of Incando established, I talked to as many of my colleagues and friends as I could. I was fortunate to find a small group of people who were at the right stage in their careers to think about such a start-up. Some left, but those who stuck around got engaged with the work and caught up in the vision and progress we were making. We all contributed as the company grew and that solidarity has sustained us through our tough times, especially before our funding was secured. We’ve grown the team very selectively- we often bring someone on board for a small project to assess fit and contribution before moving to anything more substantial. This is not scalable as we grow, but for now it has helped build an incredibly tight knit team.
In terms of setting the right culture, I try to be the boss I always wanted but did not get in my career. I invest time to share my plans and show everyone how they fit and are valuable. Keeping on top of the vision and communicating how the company is living and breathing is very important to keep people motivated. I also take it upon myself to help in my team’s career development and constantly try to keep them challenged to help them grow. Additionally, I give my team the freedom to give me honest feedback. This is not easy, but creates a wonderful dynamic where the best ideas can emerge and where we can fully take advantage of differing viewpoints.
Incando Therapeutics Team at NUHS Surgery Workshop
BCS: Why are you choosing to set up Incando Therapeutics in Singapore? Do you have plans to grow this company overseas?
Percy: Our headquarters is here in Singapore and we have branches in Hong Kong and the United States. Singapore offers a lot of advantages for our business, an international reputation for financial and IP compliance and world leading medical research and clinical trial facilities. Being resource limited, I also set out to conduct the first stages of Incando as a virtual company based out of my home here in Singapore. The professionals I gathered are located all across the world but Zoom makes it easy to run a team not only regularly, but around the clock. We are also able to take advantage of contract services, including lab services, around the world to keep our overhead costs low. Of course, when we move into our clinical stages, we will have to expand our footprint to countries with a larger patient population.
BCS: Where do you run your business operations and conduct your experiments?
Percy: Our laboratory work is conducted through collaborations and contract services with various academic and commercial partners. For our engineering, we have facilities in California and Australia. For our biology work, we have labs in Singapore, Hong Kong and the US. I still do experiments at the bench in our collaborators’ labs in NUS and find that it’s crucial to maintain and grow a research presence amongst a community of colleagues. Until we have a large team of scientists on our own, it is healthy and necessary to be part of a scientific community that is active and at work.
BCS: What would you describe as the greatest challenge for Incando Therapeutics right now?
Percy: We have grown rapidly and made a lot of progress since inception. This creates a lot of resource demands that are constantly upgrading as we progress from stage to stage. With a limited budget it is challenging to prepare for clinical stage work with preclinical resources. We’ve reached the limits of our seed stage and need to scale up in almost every regard. I’m constantly on the lookout for new connections, relationships or advisors that can bring my team what they need for the growing tasks at hand.
Fundraising is also a major issue right now. Unfortunately, we are now in a period of economic uncertainty, which makes risky long term medical ventures unattractive. However, I remain optimistic- cancer is a problem that will persist regardless of the economy, and we have a unique solution.
BCS: What are your thoughts about the funding ecosystem for aspiring start-ups in Singapore?
Percy: I think that Singapore’s funding ecosystem has grown a lot since I first arrived here 2009 and has reached a mature level for the digital, financial and logistics spaces. In contrast, little growth had been seen for health and medical companies until just recently. Because of the COVID-19 pandemic, I think there has been a renaissance of medtech and biotech funding within Singapore. Global activity in infectious disease has also led to secondary investment from institutional investors and the venture arms of multinational companies in telehealth, cancer, medical devices, and health information systems. With several home grown COVID success stories coming from Singapore, the local life science investment scene has warmed significantly and gained new players. This is very encouraging, and I hope it reaches the therapeutics sector.
I am originally from the US and grew up in the San Francisco Bay Area, the nexus of biotech. I came to Singapore because of the unique opportunity to do biology in Asia, however I quickly became frustrated by the different risk appetite within the public funding ecosystem and the lack of people entering bio-entrepreneurship. Healthcare, therapeutics, and biotech start-ups are usually long-term ventures and have a high risk of failure. However, in successful biotech and pharma communities, the risk is accepted and mitigated through shared efforts by government and private industry. Only in this way can the community grow with experience organically and keep at efforts that inherently have a high failure rate.
Singapore has all the right elements to supercharge this community. With an incredible ability to build research infrastructure and a talented pool of young scientists, there is great potential for an impactful biotech community. Unfortunately, many start-ups here tend to stall out in the valley of death. Translating research into products requires a certain expertise and this expertise is rare in Singapore. The established communities exist in Boston, San Francisco, San Diego for biotech and, Minneapolis for medtech. These types of workers require a long runway to develop their expertise and are often past a stage in their life where they can transplant their career over to Singapore or Asia. Even if they do come here, most are quite entrenched, and it is difficult to get them to contribute meaningful time to a new project. All these elements as well as a robust funding environment must be in place to stimulate more life science start-ups. Efforts to improve and grow this community have been ongoing, however I believe that a critical mass has not yet been reached.
It was difficult to find funding for Incando in Singapore. In the spectrum of life science companies, we work on therapeutics which is the highest risk class with the longest lead in time and highest price tag for development. Additionally, our approach as a drug-device combination with a long-term implant into the brain might probably the highest risk and most improbable product that anyone could possibly think of. I recognise that we are not for most investors – the risk profile is extremely high. Even so, I know that there are still life science investors out there who understand the process and are willing to fund exciting projects.
BCS: How did your previous career prepare you to be the CEO of Incando Therapeutics?
Percy: The idea behind Incando is the intersection of a number of disciplines. It was a tremendous advantage to have such a varied career as expertise in such different fields helped with the insight to put together our company. Of course, my research background was essential- especially in neurosciences. The technical side gave me the foundation for our light-based product and the functional knowledge enabled me to connect with physicians. I gained much IP, business and investment knowledge from working in the NUS Enterprise university incubator. This was put into deeper practice in my subsequent role as translational director in the Singapore Institute of Neurotechnology where I also gained first-hand knowledge about engineering, devices and the clinical process of building implants.
Beyond that basic knowledge, there has been a lot of learning on the job. One important aspect of leading a company is to the constant exposure to feedback, which is part of the creative process. My science and teaching background prepared me for these challenges- you are constantly under scrutiny, both external and from within. This has humbled me and showed me that I have a lot of growing to do. Approaching it all like a scientific experiment that needed to be improved was tremendously helpful for me. Every day, I’m thankful that my career has led me to this opportunity that has turned out to be my dream job. I get to do science; I get to engage with incredibly smart people, and I get to make my humble contribution to the benefit of humanity.
BCS: Finally, given your experience, what advice would you give to aspiring scientific start-up founders?
Percy: First off, take advantage of being in a lab. Being protected and resourced by an established university or commercial scientist is priceless. Do not take for granted the ability to get into a lab and create data. Build your evidence and then sort out the ownership or licensing rights with your parent institution. It will be difficult to share, but remember it is only the first step- you will create more data that you own as a company.
Next, scientists need to upgrade themselves mentally to be successful start-up founders. Many scientists tend to be very possessive over their work and overly concerned about authorship and attribution. You must give up the attachment to your own ideas and work more collaboratively. This is difficult but necessary. I have seen many companies go down because of scientists not letting go of ego issues.
Finally, learning how to communicate is key to leading a start-up. There are tons of people who can do technical work but being able to communicate is the differentiating factor. As a founder, I spend the majority of my time sharing my vision, networking and building relationships. You need to be able to sell your story and make it clear enough for anyone to buy into your vision- even if they don’t have scientific training. If you can do so, you will be able to find resources, build relationships, manage employees and convince investors to support you.