Chad Robins, Adaptive Biotechnologies CEO, co-founder, and chairman

More than a decade after Chad Robins and his brother Harlan co-founded Adaptive Biotechnologies to translate insights from the adaptive immune system into diagnostics and drugs, Robins, who is Adaptive’s CEO and chairman, acknowledges the company is still in early stages of fulfilling its ambitious mission: “We’ve made a phenomenal amount of progress, but we’re still just scratching the surface.”

Just how far Adaptive has to go can be seen, Robins said, in autoimmune disorders with a shared symptomatology, where a patient experiencing stomach pain or other gastrointestinal issues may not know whether they have Crohn’s, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), or celiac disease (or something else).

“What we’re trying to do is say, ‘Hey, if you have the receptors that are specific for the disease that we map, we actually then can define the disease, if you will, from the receptor,’” Robins said. “There are many diseases that we don’t even really have definition yet. We’re making good progress but there’s a very long way to go.”

Adaptive carries out immunosequencing through its proprietary immune medicine platform, developed by Harlan Robins, PhD, the company’s chief scientific officer, while at Fred Hutchinson Cancer Research Center. Harlan—who joined brother Chad in co-founding Adaptive in 2009—headed the Fred Hutch computational biology program before stepping down from the cancer center’s faculty in 2019.

Adaptive’s platform applies proprietary chemistry, computational biology, and machine learning to read the genetic code of a patient’s immune system. The platform takes the key cells of the adaptive immune system that enable the body to mount responses against antigens—T cells and B cells—extracts and sequences their genomic DNA, then identifies the receptor sequences that are contained within those cells. T cells and B cells randomly assemble different gene segments—called variable (V), diversity (D) and joining (J) genes—in a process called VDJ recombination, designed to generate antigen receptors that can collectively recognize molecules posing exogenous or endogenous threats to the body.

The sequenced receptors are mapped to the antigens they bind to, a process designed to reveal which diseases a patient’s immune system has seen or is actively fighting. The two chains from each of hundreds of thousands of T- or B-cell receptors are paired back together in parallel for therapeutic use, then characterized to determine which T-cell receptors are most effective for cell therapies, or which B-cell receptors produce the most effective antibodies against disease.

Partnering with Microsoft

Adaptive has been carrying out the mapping through its T-cell receptor (TCR)-Antigen Map collaboration with Microsoft launched in 2018, and expanded last year to study COVID-19. The partnership aims to use immunosequencing and machine learning to map sequences to diseases and disease-associated antigens. The companies reason that every disease has disease-specific antigens that could range in number from just a couple to several hundred, with a many-to-one relationship between T-cell receptors and antigens.

“Essentially we’re creating a map, disease-by-disease, of T-cell receptors to antigens,” Robins said. “This map is going to be larger than all the data combined on the World Wide Web. This is a massive, massive amount of data, because it’s estimated that there’s between 1016 and 1018 T cells in the population.”

Hence the need for machine learning in addition to chemistry and other technologies. The core of the TCR-Antigen Map is the biological data and models derived from Adaptive’s patented high-throughput immunoSEQ sequencing and MIRA (Multiplexed Identification of T cell Receptor Antigen Specificity) antigen-mapping technologies to determine all possible T-cell receptors that bind to clinically relevant antigens across diseases.

immunoSEQ is designed to sequence single chains of Y-shaped T cell receptors or B cell receptors using next-generation sequencing (NGS), enabling users to understand the quantity and diversity of T and B cells in a biological sample. MIRA maps millions of TCRs to thousands of clinically relevant antigens.

Adaptive has been carrying out the mapping through its T-cell receptor (TCR)-Antigen Map collaboration with Microsoft launched in 2018, and expanded last year to study COVID-19. The partnership aims to use immunosequencing and machine learning to map sequences to diseases and disease-associated antigens. [Adaptive Biotechnologies]
When combined with immunoSEQ, the technologies elucidate what potential diseases a patient’s immune system has seen or is actively fighting.

“If we can truly characterize those immune receptors, if we can learn how to read how they’re seeing disease, that we can create diagnostics that essentially mimic how your body is naturally diagnosing disease,” Robins said. “At the same time, if we can harness the power of those immune receptors as targeting molecules, then we can create new drugs by really harnessing the power of how your immune system is fighting disease.”

Clinical diagnostics

Adaptive has leveraged its platform in its clinical diagnostics offerings. The company’s clonoSEQ® Assay is designed to detect and monitor minimal residue disease (MRD) during and after treatment in patients with multiple myeloma (MM), B-cell acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL)—the first and only FDA-cleared assay for MRD assessment in those diseases. clonoSEQ is also in clinical validation phase for subtypes of non-Hodgkin’s Lymphoma.

In November, Adaptive received a final local coverage determination (LCD) from Palmetto GBA’s Molecular Diagnostics Program (MolDX) supporting Medicare coverage for clonoSEQ in all three cancer indications. Adaptive in September rolled out an enhanced verison of clonoSEQ for CLL, providing immunoglobulin heavy chain variable region gene (IGHV) mutation status in the same test that measures the trackable MRD sequence.

clonoSEQ clinical sequencing volume grew 47% during the third quarter, helping propel Adaptive to positive third-quarter results showing a 50% year-over-year revenue increase, to $39.467 million from $26.299 million in Q3 2020. Adaptive finished Q3 with a $55.998 million net loss, up from a $36.719 million net loss for the year-ago third quarter. However, the company reiterated earlier investor guidance that its 2021 revenue will range from $148 million to $155 million, representing 54% growth at the mid-point of the range over full year 2020 revenue.

The reiterated guidance and revenue jump led investors to buy shares of Adaptive, whose closing price climbed 7% to $36.85 on November 4, before falling back to $28.

Another clinical diagnostic, T-Detect™ COVID, is designed to detect T-Cell responses to SARS-CoV-2, and FDA-authorized for emergency use. At the IDWeek 2021 virtual conference in October, Adaptive presented data from three studies showing the potential clinical utility of T-cell testing using TCR repertoire characterization for infectious diseases.

Specifically, T-Detect COVID was shown to detect prior infection nearly 12 months after diagnosis in some patients, and was shown to distinguish natural SARS-CoV-2 infection from COVID-19 vaccine response—an important advantage over antibody tests, according to the company.

Adaptive also presented data showing TCR repertoire characterization to be nearly twice as sensitive as standard two-tiered testing at identifying individuals with early Lyme disease. T-Detect is also in signal discovery phases for ovarian cancer and GI diseases such as celiac and Crohn’s.

Broadway debut

Adaptive recently opened a business development office in New York City near Times Square, at 1540 Broadway. Between 20–30 full-time staffers out of Adaptive’s 850 employees will be based in New York, Adaptive’s first on the East Coast.

“We have an increasing number of employees who are East Coast based in New York, and we wanted to make sure that they had a physical presence out here,” Robins said.

That presence, he said, offers Adaptive two advantages. One is the opportunity it affords to host meetings with biopharma or academic partners at its own facility. And the other advantage?

“It’s my opinion that we’re better when we’re together, even with some of the remote work flexibility that we do have.” Robins said. “There’s really no substitute for that in person collaboration and whiteboarding.”

Most Adaptive employees are based at its Seattle headquarters, where Robins and other executives in September joined Washington state Gov. Jay Inslee (D) in cutting a ceremonial ribbon formally opening the company’s new 100,000-square-foot HQ in Seattle’s South Lake Union section, owned by Alexandria Real Estate Equities.

Adaptive also maintains a field staff of medical liaisons, key account managers, and sales reps, as well as 45–50 employees in South San Francisco, CA—where the company leases about 50,000 square feet at Genesis SSF-North Tower for its cellular immunology and innovation group.

That site has expanded, said Sharon Benzeno, PhD, chief business development officer and leader of the drug discovery group, as a result of Adaptive’s three-year-old collaboration with Genentech.

Up to $2 billion

Sharon Benzeno, PhD, Adaptive Biotechnologies Chief Business Development Officer and leader of the Drug Discovery group

Genentech and Adaptive launched an up-to-$2 billion collaboration in 2019 aimed at developing therapeutics designed to identify specific immune cells to develop into cell therapies in oncology. Through the partnership, Genentech has applied Adaptive’s TruTCR® process, designed to characterize TCRs against shared antigens for use in the development of those cell therapies.

At deadline, Adaptive and Genentech have developed a “shared” product using off-the-shelf TCRs identified against cancer antigens shared among patients; and a personalized product using patient-specific TCRs identified by real-time screening of TCRs against cancer antigens in each patient.

For the shared product, Adaptive says it is assessing efficacy and safety data with Genentech to enable a decision by year-end to advance a lead product into early development. In November, Adaptive completed a data package for the second TCR to be submitted to Genentech for selection of that shared product, Benzeno said.

As for the personalized product, Adaptive plans by year’s end to screen blood from more than 60 cancer patients in a proof-of-concept study designed to identify T-cell receptors specific to those patients. “Next year, we’ll start further refining defining and optimizing the second prototype to ultimately aim for speed to the clinic,” Robins said.

In addition to Genentech, Adaptive is partnering with Nykode Therapeutics (which changed its name from Vaccibody on November 23) to design and develop novel SARS-CoV-2 vaccines based on virus-specific T-cell epitopes identified by Adaptive’s platform. The companies have not disclosed the value of their partnership, announced in July.

Nykode has announced the launch of a two-arm, Phase I/II open label, dose escalation, and dose expansion study (NCT05069623) designed to assess the safety, reactogenicity, and immunogenicity of two DNA plasmid COVID-19 vaccine candidates—VB10.2210, a vaccine jointly developed by the companies using Adaptive’s T cell RBD epitope, and VB10.2129, a Nykode receptor-binding domain-only vaccine. Data from the 160-participant study is expected to emerge in the late spring or early summer of 2022.

“The trial actually is to enroll previously vaccinated individuals, with the idea that these next generation vaccines [Nykode] is advancing are absolutely more of a universal booster, as an add-on to existing vaccines,” Benzeno said.

“That’s our first example of extending the platform in vaccines and specifically T-cell based vaccines that we look to do in other disease areas.”

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