The concept of an antibody drug conjugate is straightforward enough: a cancer-killing drug payload attached to a targeting antibody that directs the molecule to cancer cells. Though these targeted therapies have established a place in cancer care, one of their shortcomings is that some of that drug slips out prematurely, leading to toxic effects in healthy tissue. The founders of Mythic Therapeutics say their technology ensures that more of an ADC’s drug payload reaches tumors, potentially making these therapies more effective and more accessible to a wider range of patients. The startup is now out of stealth with $103 million to build its case.
The Series B round of funding announced Wednesday was led by Viking Global Investors.
Scientists have been researching ADCs for decades, and so far, 11 drugs in this class have been approved by the FDA. The first one, the Pfizer acute myeloid leukemia drug Mylotarg, was approved in 2000 but was dogged by toxicity concerns that chilled the ADC field for years.
Alex Nichols, CEO and co-founder of Waltham, Massachusetts-based Mythic, said toxicity has stopped ADCs from reaching their full potential. Despite being designed for targeted delivery, he said research has shown that just 5 to 10% of the drug payload reaches the tumor. The rest of the dose goes to healthy tissue, where it sparks side effects, or it’s just degraded by the body providing no therapeutic benefit. Mythic’s technology increases the dose of the drug taken up by a tumor, increasing an ADC’s therapeutic index—the dose range within which a drug is effective without also causing adverse events.
“More drug goes where you want it, less where you don’t, and you end up with an increase in therapeutic index,” Nichols said.
The way Mythic’s technology works is by changing the way an ADC interacts with its target, said Brian Fiske, co-founder and chief scientific officer of the startup. As a consequence, the drug has an increased on-target effect, which in turn decreases the amount of toxic drug that reaches healthy tissue and sparks off-target effects, he said. The technology, called FateControl, is compatible with the drugs payloads and linkers that are currently used in ADC drugs. Furthermore, FateControl opens up ADCs to new targets that perhaps were not feasible for ADCs previously, Fiske said. He added that the technology can broaden the pool of patients that can be treated with this type of drug.
Lung cancer is Mythic’s first disease target. Nichols said that this type of cancer is a good match for the startup’s technology, and it also offers the potential to expand the use of ADCs. Of the currently available ADCs, none are approved for lung cancer. Fiske said the company has found other targets that are a good match for FateControl, and the company is pursuing them as it develops its pipeline. The targets in lung and other types of cancer are not disclosed, but Nicols said they are “both precedented and novel targets.”
Nichols and Fiske are both veterans of other biotech startups; Nichols was on the founding team of Cogen Therapeutics (now named Repertoire Immune Medicines) and Fisk co-founded and was chief technology officer of Ohana Biosciences. Prior to starting Mythic, both worked at venture capital firm Flagship Pioneering.
Mythic’s approach to ADCs sprang from a brainstorming session at Nichols’ dining room table. Starting with a blank notebook, Nichols said he and Fiske started writing down ideas about how to approach cancer. Fiske said that they noticed that targeted therapies have a great impact on some, but these therapies aren’t accessible to most patients, who instead have surgery, radiation, or chemotherapy as their main treatment options. The two settled on the idea of trying to find ways to expand the number of cancer patients who could be treated with targeted therapies. With that focus, they turned to cancer experts, which in turn led them to realize the untapped potential of ADCs. Nichols and Fiske co-founded Mythic in 2017.
Mythic’s launch comes amid a resurgence of the ADC field. Of the 11 ADCs that are currently FDA approved, six have reached the market in the last two years. The newest drug in this class is Tivdak, a Seagen drug approved in September for treating cases of recurrent or metastatic cervical cancer. That decision followed the April approval of Zynlonta, an ADC Therapeutics drug developed for treating diffuse large B-cell lymphoma.
As these new ADCs enter the market, a growing number of new companies are cropping up with the goal of following them. Venture-backed ADC startups that have launched this year include Adcendo, Adcentryx, and ProfoundBio. Cambridge, Massachusetts-based Pyxis Oncology has a pipeline of three ADC candidates along with ADC technology licensed from Pfizer. In October, Pyxis’s IPO raised $168 million to advance those molecules into human testing.
Competition to Mythic could come from one of the already approved ADCs that finds an additional application in lung cancer. Enhertu, an ADC from AstraZeneca and Daiichi Sankyo was approved nearly two years ago for treating breast cancer that’s positive for the protein HER2. In September, the partners reported Phase 2 data showing that addressing the same target with its ADC in non-small cell lung cancer also showed a “robust and durable” tumor response. Results from the study were published in the New England Journal of Medicine.
Nichols and Fiske initially bootstrapped Mythic before raising seed financing in 2018. Venrock led a 2020 Series A round. Nichols declined to say how much the startup has raised in total since inception. New investors in Mythic include Venrock Healthcare Capital Partners, Foresite Capital, Perceptive Advisors, and Highside Capital. Earlier investors also joining the latest financing include Venrock, First Round Capital, OMX Ventures, Lifeforce Capital, and Refactor Capital.
With the Series B cash, Mythic aims to advance its lung cancer ADC into clinical trials. That program is currently in the preclinical research that could support the filing of an investigational new drug application, but Nichols declined to project when clinical testing could start. He did say that the financing will support that lead program through an early proof-of-concept signal in Phase 1 testing.
Though cancer is Mythic’s current focus, Nichols said FateControl could be used to develop drugs for other therapeutic applications. ADCs have also been studied in immunology, but Nichols declined to specify the areas that the startup might pursue, on its own or with a partner. It’s too early, and the company isn’t ready to go into detail about that research, Nichols said.
“In general, any potential application where you want to deliver a cargo using an antibody is one where our technology can be beneficial,” he said.
Image by Flickr user Ed Uthman via a Creative Commons license
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