Welcome to Biotech Spotlight, a series featuring companies with a breakthrough technology. Today, we’re looking at Candel Therapeutics, a late clinical-stage biopharmaceutical company that specializes in fighting cancer with oncolytic viral immunotherapies.
In focus with: Dr. Paul Peter Tak, CEO of Candel
Candel's breakthrough technology: The mechanism of action of Candel’s oncolytic viral immunotherapies is unique because it combines both an anti-tumor cytotoxic component and an immune-stimulatory component. Together, these modalities lead to an “in-situ vaccination” effect against the tumor.
Why it matters: Like a candle, the company says its oncolytic viral immunotherapies “light up and empower” the immune system to fight cancer at the point of delivery. Using its genetically modified adenovirus-based platforms, Candel is able to calibrate its treatments for a variety of solid tumors, including prostate, brain, lung and pancreatic cancers, to precisely deliver therapy to each cancer being targeted. If successful, the approach could improve tolerability, quality of life, and potentially, survival rates.
The company also has another trick up its sleeves: a discovery platform that can be leveraged for several indication areas that Tak says can create candidate-selected molecules in 6 to 12 months.
Tak’s leadership philosophy: Empowering leadership.
At a glance: Hot on the trail of a newly minted IPO, and with a burgeoning pipeline of therapeutics, a new discovery platform and a management philosophy focused on sustainable success, Tak has Candel positioned to successfully develop immunotherapies that could potentially revolutionize oncology. With two investigational medicines in six clinical trials ongoing — Tak believes Candel’s process will lead to therapies that exhibit systemic, durable immune response against solid tumors, with the potential to change disease outcomes across a variety of indications.
The company’s virus-based platforms, resulting in genetically engineered gene constructs that are delivered to the site of the tumor to minimize impact on healthy tissue, while maximizing the patient’s immune response to fight the tumor, allow for treatments to be calibrated to each cancer.
To learn more about their unique approach, we caught up with Tak, a PharmaVoice 100 honoree.
PharmaVoice: What makes Candel’s oncology science different?
Dr. Paul Peter Tak: We are developing immunotherapies that induce immunogenic cell death in cancer cells at the site of injection, unmasking tumor neo-antigens within an activated microenvironment.
You’ve had a busy 12 months; can you share some of the highlights?
The company is in a great place to deliver on our mission. We’ve basically doubled the size of the company to around 65 people, brought together a high-performing executive team as well as a talented team throughout the organization to form a very strong culture characterized by both freedom and accountability — what I call empowering leadership. This is a key component to success. People are behind the mission to change the lives of patients. While we want to create value for shareholders, we also need to create value for patients and employees.
Last summer we did an IPO, which gave us proceeds that we need to deliver on multiple clinical inflection points. And this year is going to be super exciting in that respect.
We expect to get clinical data for CAN-2409 for non-small cell lung cancer — a huge clinical unmet need — and a big business opportunity for the company. We are focused on patients who have failed first-line treatments, including chemotherapy and immune checkpoint inhibitors. These patients basically have no real therapeutic options; they have progressive disease or stable disease, which means there's no further improvement or they have a complete refractory disease. We are looking at these patients in real time, in an open-label clinical trial because there are no placebo effects expected in this population. Based on the kinetics of the immune response, we expect to see the first clinical response in small numbers of patients no later than June of this year. This is potentially the first value creating inflection point this year for Candel.
What else is on the agenda for 2022?
We are looking at two other data inflection points in the clinic this year — and in the end, it's all about the data. We are looking at a read out for our indication for a high-grade glioma form of brain cancer, again a huge unmet need. The median overall survival rate is 15 months despite all the therapeutic options, including neurosurgery, chemotherapy, radiotherapy, and so on. We've presented positive phase 2a clinical trial data in the past, and the data this year will be from a study in combination with BMS’s immune checkpoint inhibitor. Generally, I would say immune checkpoint inhibitors have been disappointing in this field. But based on a well-established mouse model, we have reason to believe that there might be synergy that we can improve even further the effects of CAN-2409 lead compounds. We expect to see initial clinical activity in the fourth quarter of this year.
The third data point is another update with recurrent high-grade glioma. These patients have failed everything, so their prognosis is even worse. They're completely therapy-resistant. With CAN-3110 we can provide oncolysis through tumor replication specifically in Nestin expressing cancer cells, like high-grade glioma cells. We presented initial phase 1b clinical activity data in an oral presentation at ASCO last year. We are in early days, but the data are very encouraging. The PI is the head of neurosurgery at the Brigham and Women's Hospital, one of the leaders in the world in this field. And in December of this year, we will have new clinical data from a new cohort of patients and more extensive biomarker research.
And in December of this year, with the other asset in the clinic called CAN-3110, we will have new clinical data from a new cohort of patients and more extensive biomarker research.
So that's all great — three shots on goal.
Can you tell me about the discovery platform that you created?
Sure, we have not spoken much about this in the past. Before Candel, I worked at Flagship Pioneering, an organization that focused on discovery platforms. Now at Candel, in stealth mode we created a discovery platform focused on herpes simplex virus — HSV — technology. Through the platform we call enLIGHTEN, we can create, in a very flexible way, a new HSV gene construct in a short period of time.
In the same way Moderna used mRNA technology to make a new vaccine in a very short period of time, we can use engineered oncolytic HSV to create new candidate-selected molecules within six to 12 months, including the preclinical package to modulate the tumor microenvironment in solid tumors. And we do this using sophisticated, systematic approaches, including a strong focus on human biology and artificial intelligence to deeply understand what’s going on. I’m not aware of any comparable systematic discovery platform in the space of oncolytic virus immunotherapies among our competitors or colleagues, so this is another potential important value driver for the company. And we hope to see the first selected candidate molecules this year.
How are you structuring the company for success?
In terms of development, we do quite a lot of that ourselves. In a way, part of the organization is like a CRO; going forward, we will outsource more than we've done in the past. In terms of discovery, it’s almost the other way around. We try to own what we need to own. We acquired a small biotech company that can do everything with HSV. My background is in immunology and drug discovery and drug development. For anything that is standard, like specific animal models, we outsource so we can switch it on and off in a very systematic way, this way we don’t need a huge organization — we only own what we want to own. We are very agile, and in a way, we are a micro-pharmaceutical company, as I call it. The enLIGHTEN discovery platform allows us to feed and fill the pipeline, and leverage the huge clinical and regulatory experience that we have developing oncolytic virus immunotherapies.