Original Article By Galym Imanbayev and Jonathan MacQuitty – on Medium
Today, AstraZeneca announced its agreement to acquire TeneoTwo, a subsidiary of TBio which is managed by Ancora Biotech, for $100M upfront as part of a total transaction value of $1.265B including milestones. The acquisition will accelerate the development of TeneoTwo’s CD19/CD3 T-cell engager for B-cell malignancies, including large B-cell lymphoma and follicular lymphoma. To us, the acquisition ultimately expedites the path to improving patient lives across these serious areas of unmet clinical need. We congratulate both the Ancora and AstraZeneca teams on this achievement.
While this transaction comes less than a month since Lightspeed’s investment in Ancora’s Series A, it is part of a longer narrative we described in a previous post. Over the past 12 months, the same team behind Teneobio and Ancora have led three acquisitions — TeneoOne to Abbvie, Tenebio to Amgen, and now, TeneoTwo to AstraZeneca. Such a velocity of valuable deal-making, even in this market environment, underscores the value of the platform, quality of assets and the thoughtfulness behind the clinical strategies that the Ancora team pursued for TeneoTwo, and now, continues to leverage for TeneoFour and TeneoTen. While we certainly valued TeneoTwo, central to our investment thesis in Ancora was also the potential of TeneoFour and TeneoTen — the ability to leverage the existing platform to address high unmet needs outside of oncology.
TeneoFour aims to target the critical role of CD38 in cellular metabolic processes, particularly NAD metabolism. It is well known that NAD (nicotinamide adenine dinucleotide) is a cofactor of key enzymes in a healthy cell including glycolysis and multiple other critical redox reactions. Until recently, how and which specific metabolic pathways regulate NAD levels has been unclear, despite its broad centrality to disease including age-related NAD decline, which is viewed as an underlying process of multiple conditions of aging. Among the new insights into the biology of NAD regulation, the active role of CD38 has been evidently shown in mediating age-related NAD decline, including acting as the main enzyme metabolizing the NAD precursor NMN. Other hypotheses, such as the role of PARPs (poly(ADP-ribose) polymerases) have failed to meet the same level of evidence.
TeneoFour aims to inhibit CD38, and thus potentially drive higher NAD, improve mitochondrial health, reduce hyperinflammation and reverse fibrosis. Pairing the recently bolstered biological evidence of CD38 with Ancora’s platform in a biparatopic antibody targeting CD38 presents an exciting opportunity to target immunometabolism as the gate to a variety of high value, unmet clinical needs for patients. TeneoFour has started to enroll patients in a Phase 1 dose escalation study in healthy volunteers.
TeneoTen is an anti-HBsAg x CD3 antibody intended to treat patients with chronic hepatitis B infections. Today, more than 250 million individuals are infected with HBV. Those with chronic infections have an up to a 40% lifetime risk of developing liver cancer. Unfortunately, no curative option is available for chronic HBV due to existing treatments’ inability to target the persistence of covalently closed circular DNA in the nucleus of hepatocytes. Despite these challenges, T-cell mediated treatments may hold potential in chronic HBV, as allogeneic bone marrow transplantations have been shown to be curative. T-cell mediated mechanisms are also critical in the resolution of acute HBV infections.
TeneoTen, which is currently preclinical, aims to leverage the potential of a T cell-mediated approach by leveraging its unique anti-CD3 arm and multivalent antigen arms to effectively target cells infected with HBV. We believe this robust modality and its advantages across reactivity to multiple serotypes, high expression and attractive manufacturability present an promising opportunity for a critical unmet need for millions of patients worldwide.
Ancora is embarking on an ambitious journey with TeneoFour and TeneoTen. We welcome those entrepreneurs and scientists with expertise and interest to reach out to Lightspeed. We focus on forming deep partnerships with savvy founders who can utilize quality technology and strategic drug development to translate top science into patient impact. Ancora is a powerful combination of all these qualities and we look forward to continuing to support the team in this next chapter.