Tao Fu, Attovia Therapeutics co-founder and CEO

A developer of nanobody-based drugs focused on immunology and oncology said it plans to bring its lead candidate into clinical proof of concept, build a pipeline of treatments, and advance its tech platform using the $60 million in Series A financing it has just raised.

Attovia Therapeutics has launched as a spinout of Alamar Biosciences, a precision proteomics company specializing in disease detection. Alamar teamed up with the lead investor in the financing, Frazier Life Sciences to form Attovia, whose name is a portmanteau for its Attobody™ antibody engineering platform, and the word “vitality.”

Using Attobody, Attovia has generated a lead candidate about which the company isn’t saying much, except that it is designed to treat undisclosed immune-mediated diseases.

“We plan to actually have our lead program be in the clinic by 2025,” Tao Fu, Attovia’s co-founder and CEO, told GEN.

Attovia develops “biparatopic” nanobodies or “Attobodies” consisting of two single heavy chain only (VHH) antibody fragments connected by a linker. Each VHH binds an epitope in a functional domain on a target protein; each Attobody binds two epitopes at the same time.

The Attobodies generated by the platform are small format binders that show ultra-high affinity, enhanced internalization, and fast tissue penetration. These properties, according to Attovia, make the Attobodies ideal binders for hard-to-drug targets such as G-protein-coupled receptors (GPCRs), and enable broad applicability across modalities that include antibody-drug conjugates, radioconjugates, or multi-specific biologics.

The Attobody platform is designed to work by screening VHH pairs with a linker library, generating a diverse set of candidates with what Attovia says is higher affinity, selectivity, and epitope coverage than traditional screening methods.

Dialing up or down

The platform also allows the affinity of the Attobodies to be dialed up or down to achieve specificity—a proprietary approach that according to Attovia dramatically increases the number of leads, increases epitope coverage, and creates the potential for agonistic and antagonistic activities.

Attovia reasons that the biparatopic binding mode of its Attobodies, together with its high-throughput approach to discovering binders, will significantly expand its universe of druggable epitopes and targets for new treatments.

“What we’re really trying to do is not only do a nanobody, but a biparatopic nanobody,” Fu said. “There are several potential advantages of doing that, so we’re really trying to take advantage of the technology and trying to find some killer applications.”

Attovia Therapeutics has illustrated how its Attobody™ antibody engineering platform develops “biparatopic” nanobodies consisting of two variable domains of single heavy chain (VHH) antibody binders connected by a linker. One binder engages an epitope in a functional domain on a target protein, while the other engages a target selective epitope. [Alamar Biosciences]
Those potential advantages, Fu said, include:

  • Enhanced efficacy and target selectivity based on high affinity and specificity driven by paratopic binding and binder optimization.
  • A tunable half-life that allows for flexibility in optimizing pharmacokinetics and pharmacodynamics (PK/PD) to achieve an ideal therapeutic index. The platform allows the affinity of Attobodies to be dialed up or down to achieve specificity.
  • Higher success rates resulting from the expanded diversity of epitopes and greater number of druggable leads enabled by the smaller size of the nanobodies.
  • Shorter development timeframes resulting from a simpler and thus faster manufacturing process.

Those timeframes can be shortened from the typical 9–12 month antibody development period, Fu said, since the affinity maturation process is not needed.

“You’re cutting basically a few months for this discovery process, which is very valuable in drug development,” Fu said. “Time is money in our business.”

Nanobody success

Attovia isn’t the only company that sees advantages to developing new drugs based on small format nanobodies.

Acelyrin and Affibody in March reported positive data for their lead candidate, the small protein inhibitor interleukin-17A (IL-17A) inhibitor izokibep in an open-label part of a Phase IIb/III trial (NCT05355805) in moderate-to-severe hidradenitis suppurativa (HS) and uveitis.

During a late-breaking presentation at the 2023 American Academy of Dermatology (AAD) Annual Meeting, a clinical team led by Kim A. Papp, MD, PhD, of Probity Medical Research showed that treatment with izokibep led to high orders of HS clinical response at 12 weeks: 71% of participants achieved “Hidradenitis Suppurativa Clinical Responses (HiSCR) 50,” defined as at least a 50% reduction from Baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count.

Fifty-seven percent achieved HiSCR75 (at least a 75% reduction), 38% achieved HiSCR90 (at least a 90% reduction), and 33% achieved complete 100% reduction or HiSCR100—a response not previously reported for any agent in this timeframe, according to Affibody, which has licensed development and commercialization rights for izokibep to Acelyrin in most of the world except some Asian countries, where those rights are held by Inmagene Biopharmaceuticals.

That clinical success helped Acelyrin set the stage for a successful initial public offering (IPO) last month in which it sold 34.5 million shares at $18 a share. Acelyrin raised an eye-popping $573.7 million in net proceeds—no small feat given the declining IPO market seen in the first quarter and during last year.

Last year, researchers from Australia and Singapore published a study showing that the biparatopic nanobodies they engineered to bind the receptor-binding domain (RBD) of SARS-CoV-2 using a synthetic yeast display library effectively neutralized the virus: “Biparatopic nanobodies offer a way to rapidly generate powerful viral neutralizers with enhanced ability to control viral escape mutants.”

Building a pipeline

Fu added that Attovia is working on several additional potential candidates, with the goal of building a pipeline of biparatopic nanobody-based treatments. The tech can work beyond immunology and oncology—though if Attovia expands to other indications, it will do so through collaborations with other companies.

“We have actually gotten quite a bit of inbound inquiries already on certain modalities and applications. It’s too early to comment on those,” Fu said.

“As a small company, we can’t focus on everything. We will have to have a narrower scope of work for our internal effort, but we are also planning to do business development, through partnerships where we work with other companies and help them build binders to their targets of interest,” added Fu, who is also a Venture Partner with Frazier.

Frazier led the $60 million Series A financing, joined by venBio and Illumina Ventures. venBio is a life science venture capital firm that focuses on novel therapeutics for unmet medical needs. Illumina Ventures is a genomics and precision health venture investment firm drawing upon a strategic relationship with Illumina but managed separately from the sequencing giant.

In connection with the financing, Jamie Topper, MD, PhD, managing partner at Frazier, and Aaron Royston, MD, managing partner at venBio, will join Attovia’s board, whose members include Fu.

Fu has more than 25 years of biopharma executive experience, including leadership roles at Zai Lab, Portola Pharmaceuticals, Bristol-Myers Squibb, and Johnson & Johnson. Joining Fu on Attovia’s leadership team are Petter Veiby, PhD, CSO; Hangjun Zhan, PhD, CTO and Zaneta Odrowaz, PhD, CBO.

While the C-suite has been filled, Attovia is still recruiting staffers, most of them in research positions, Fu said. The company aims to grow to about 20 people by the end of the year.

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