Ancora: Advancing antibodies from the lab to patient treatments

The first monoclonal antibody was approved in the ’80s to suppress the immune system of patients receiving organ transplants. The mAb used mouse proteins, however, and triggered harmful side effects. Rather than giving up on the field, researchers developed novel ways to generate antibodies in animals that would be safe for humans.

Now mAbs and a wave of next-generation antibody therapeutics, called bispecifics, are approved to treat diseases ranging from cancer to autoimmune conditions. Along this journey, Roland Buelow, who was founder and CEO of Lightspeed portfolio company Teneobio, has been a pioneer in antibody research for much of the field’s evolution from longshot idea to life-saving treatment.

Now as CEO of Ancora Biotech, Roland is advancing three bispecific antibody products, two of which are already in the clinic, that aim to offer safer, more effective treatments to a wide variety of patients. He is joined by Ben Buelow, MD as CMO and Wim Van Schooten as CSO, rounding out a tight team with a series of prior successes together.

Lightspeed is pleased to co-lead Ancora’s $60 million series A today along with SR One, which will fuel the clinical development of the antibody trio. The lead bispecific has the potential to be a best-in-class cancer treatment, and the other two could be important potential treatments for inflammatory disorders and chronic hepatitis B, respectively.

Roland led two antibody companies before Ancora, both of which saw high-profile takeouts, and now he and his team are back for an encore.

Of rats and antibody research

Roland has a proven track record of developing and closing deals on antibody innovations, and Lightspeed has built a strong relationship with Roland by investing in his discoveries.

As CEO of Open Monoclonal Technology, Roland helmed the team behind the UniRat, a transgenic animal model that expresses human heavy chain antibodies. The company, but not the UniRat, was acquired by Ligand Pharmaceuticals for more than $175 million, which gave Roland the opportunity to take his platform and build another company: Teneobio.

Roland and his team then began developing multi-specific antibodies with the UniRat, and in 2016, Lightspeed led Teneobio’s series A, with Jonathan MacQuitty, PhD, joining the board. The strength of the platform and assets helped Teneobio close several deals, which meant the series A was the only private financing the company required.

Teneobio generated about 10 heavy chain-only bispecific antibody therapeutic candidates and their efficacy and safety profiles, especially when compared with conventional scFv-based bispecifics, attracted major pharma attention. Last year, AbbVie bought one candidate, and a few months later, Amgen acquired Teneobio for $900 million upfront and up to $1.6 billion in milestones.

But not all of the products fit into Amgen’s clinical pipeline, leaving three assets — which Roland fondly calls the TeneoBabies — to be spun into Ancora.

While Lightspeed often invests in early-stage preclinical programs, our past relationship with Roland and his team, their expertise in antibody innovation and deals, plus the appeal of having two programs already in the clinic made the investment opportunity one we could not pass up. The strength of the Ancora team, combined with the opportunity potential of the wide range of indications the company is pursuing, ultimately led to Lightspeed co-leading the series A, with Galym Imanbayev, MD, joining the board.

Meet the candidates

Ancora’s lead product, TNB-486, is a bispecific T cell engager that targets CD19 on cancer cells and binds to CD3 on T cells. This type of therapeutic, which arms a patient’s immune system to focus its attack on cancer cells, is one of the most promising approaches in immuno-oncology, but difficult-to-manage side effects including cytokine release syndrome (CRS) and neurotoxicities have prevented the treatments from becoming more widely used.

To overcome safety concerns, the company developed a novel CD3 binding region that binds to T cells with a low affinity, stimulating them in a more physiological fashion that is less likely to cause excessive CRS. TNB-486 is in a Phase I study in patients with B-cell lymphoma, who are in dire need of safer, more effective treatments.

Ancora’s second program, TNB-738, is an anti-CD38 enzyme inhibitor currently being tested in healthy volunteers. Due to CD38’s critical role in cellular metabolic processes, the antibody could be broadly applicable in inflammatory, metabolic, and fibrotic diseases.

The third candidate is scheduled to enter the clinic in 2024. The anti-HBsAg x CD3 antibody is intended to treat patients with chronic hepatitis B infections, which Lightspeed sees as a huge opportunity to help patients because there is no curative HBV treatment. Worldwide, more than 250 million individuals are infected with HBV, and those with chronic infections have up to a 40% lifetime risk of developing liver cancer in their lifetime.

The potential impact of these assets is a testament to the technology, team and their ambition to improve and save patient lives. We at Lightspeed are thrilled to partner with the Ancora team as they execute on this shared mission.

— By Galym Imanbayev and Jonathan Macquitty