Teneo’s heavy chain success keeps on delivering

Yesterday’s takeout of Teneotwo came amid notable big pharma interest in the geeky science behind heavy chain-only antibodies.

Even in a biotech market downturn smart science can win through, as the father-and-son team that founded the Teneo group of companies has shown. And few have played the biotech game better: the private enterprise has secured several licensing deals, the takeover of Teneobio by Amgen, and as of yesterday the sale to Astrazeneca of a separate entity, Teneotwo.

Many will note that there are at least two other carved out companies that are available for acquisition, Teneofour and Teneoten. But what has turned Teneo into such a must-have asset? For the answer you have to go back to the scientific basis on which Teneobio had been founded in 2009, namely the discovery and generation of heavy chain-only MAbs.

Typical human MAbs comprise heavy and light chains, but engineering novel versions of these, especially those with multiple binding domains, causes problems in that the correct light chain does not always pair with its desired heavy chain. Eliminate the need of a light chain, however, and you eliminate this fundamental problem.

Teneobio achieved this by genetically engineering rats in which it could generate fully human antibodies that had multiple antigen-targeting domains while comprising just a heavy chain.

Its other masterstroke came about because Teneobio decided that current T-cell engagers tended to use outdated T cell-anchoring CD3 binders that were great at inducing cell killing, but which also triggered massive cytokine release and toxicity.

Thus the group developed a new anti-CD3 with better properties that it coupled with the heavy chain tumour-binding domains. This was employed in TNB-383B, the anti-BCMA asset Teneobio licensed to Abbvie in 2019, TNB-585, the anti-PSMA lead at the time of Amgen's acquisition of Teneobio in 2021, and TNB-486, the anti-CD19 T-cell engager spun out into Teneotwo, which Astra bought yesterday.

Carving up the Teneo stable
Asset Target Status Ownership
JNJ-75348780 CD22 x CD3 Ph1 in leukaemia/lymphoma J&J, lead arising from of 2018 discovery deal (terms undisclosed)
Unnamed ? Unclear Unclear; 2018 discovery deal with Tesaro ($10m u/f, now part of GSK)
TNB-383B BCMA x CD3 Ph1 in multiple myeloma Teneoone, licensed to Abbvie in 2019 ($90m u/f), bought out by Abbvie in 2021 (terms undisclosed)
TNB-585 PSMA x CD3 Ph1 in castrate-resistant prostate cancer Teneobio, bought by Amgen in 2021 ($900m u/f); technically the deal involved acquisitions of Teneothree, Teneofive, Teneosix, Teneoseven, Teneoeight & Teneonine
TNB-409 IL-2R agonist Preclinical
TNB-928b FRa x CD3 Preclinical
Unnamed 5T4 x CD3 Preclinical
Unnamed CD79b x CD3 Preclinical
TNB-625 Possibly polyomavirus Preclinical
TNB-486 CD19 x CD3 Ph1 in lymphoma Teneotwo, bought by Astrazeneca in 2022 ($100m u/f)
TNB-738 CD38 inhibitor Ph1, potential in autoimmune disease Teneofour (Ancora Biotech)
Unnamed HBV x CD3 Preclinical Teneoten (Ancora Biotech)
Source: company filings, scientific papers, Evaluate Pharma & Linkedin.

It is remarkable how many bites at this technology the Teneo team managed to engineer. It is not clear why TNB-486 was kept out of the Amgen/Teneobio transaction, but the move now looks like deal-making genius; it is possible that Teneobio was already fielding calls about TNB-486 back in 2021, and at the same time Amgen – which already had the similarly acting Blincyto – was not interested.

It also seems that Amgen saw the Teneobio takeout as a technology play, and bought into the heavy-chain MAb model rather than just the pipeline assets.

A final point is Teneobio’s early reliance on grant funding – an approach extolled by its then-chief medical officer, Ben Buelow, at the 2020 Non-Dilutive Funding Summit. This might have limited the VCs that bought into Teneobio and given the group a simplified ownership structure that ultimately proved more conducive to takeout.

Either way, Mr Buelow and his father, Ronald Buelow (former chief exec of Teneobio), now run Ancora Biotech, a group that oversees Teneofour and Teneoten. These two start-ups focus respectively on TNB-738, a CD38 enzyme inhibitor, and an unnamed anti-HBV T-cell engager.

The Buelows have already played a blinder. Should either of these two remaining Teneo businesses end up being acquired they will have written their names into biotech history.

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