Interview – OSE Pharma gets back-up for Tedopi

OSE Pharma has wasted little time since floating on Euronext Paris a year ago, this week using its public stock to effect a €31m ($34m) takeover of the private French biotech Effimune in a bid to fill out its early-stage pipeline.

The scientific rationale is clear: “We are in T-cell activation with our project [Tedopi], and they are in regulation,” OSE’s co-founder and chief executive, Dominique Costantini, tells EP Vantage. This points clearly to a combinatorial approach, and some might also see Effimune as a way to hedge OSE's Tedopi bet with a plan B.

OSE has good reason to be cautious: Tedopi is a therapeutic cancer vaccine – a notoriously failure-prone approach as a monotherapy – and targets lung cancer, an indication where the revolutionary advent of the checkpoint inhibitors Keytruda and Opdivo has caused problems for many following competitors.

The company argues that Tedopi holds considerable promise. “Previous cancer vaccines have focused on one tumour antigen; we are working on neoepitopes,” says Ms Constantini. A neoepitope is a patient-specific mutated region in a known antigen, capable of binding T-cells and triggering immune response.

“We have seen survival in phase II that correlated with T-cell response in very poor-prognosis patients.”

Checkpoint combinations

This finding had two effects: firstly Tedopi was moved into a phase III trial, Atalante 1, this month, and "secondly we started to think about combinations”, says the chief exec. Initially non-exclusive alliances will be sought to combine Tedopi with Keytruda, Opdivo or developmental agents, before OSE turns to combos with Effimune's Effi-dem, a preclinical anti-ckeckpoint MAb.

Ms Constantini will not disclose what checkpoint Effi-dem hits, but says this is not a T-cell target, instead being associated with myeloid cells and tumour-associated macrophages. Thus Effimune’s two lead assets – an anti-CD28 agent in phase I for rheumatoid arthritis and an anti-CD127 MAb for other autoimmune diseases – are not OSE’s primary focus.

In a way these two are now self-financing. OSE expects Johnson & Johnson to exercise an option on the former in the second half of the year, triggering a typical up-front, milestone and royalty deal. The latter is in development by a €20m consortium, €9m of which is funded by Bpifrance, a public French body.

The anti-CD127 MAb is a future partnering opportunity “that would clear the way to work on Effi-dem”, says Alexis Peyroles, OSE’s finance chief in charge of business development.

Cancer vaccine

Tedopi is an off-the-shelf vaccine comprising nine synthetic epitopes addressing five well-known tumour-associated antigens and one T-helper epitope.

It is injected subcutaneously, and it is hoped that antigen presentation can stimulate a sufficiently robust T-cell response. The epitopes are HLA-A2-restricted, meaning that they are capable of being presented in A2-positive patients – around 45% of the Caucasian population.

Asked about evidence of efficacy Ms Constantini points to a phase II trial, in 63 NSCLC patients who had failed one to six lines of chemo: “We saw survival of 17 months; that’s the rationale for us to do the phase III.”

Still, caution must be exercised in interpreting this result. The trial was designed to show a survival benefit in A2-positive versus A2-negative patients – which it did numerically, though without statistical significance – and not for Tedopi versus control.

Thus OSE relies on separate NSCLC studies showing 11-month survival for checkpoint inhibitors, and compares against this historical control – an approach that is informative but not statistically sound.

Indeed, it took over seven years from the phase II data’s publication in 2008 before OSE was able, armed with the IPO cash, to start the phase III Atalante 1 trial. Atalante 1 aims to show a survival benefit for Tedopi against standard chemotherapy solely in A2-positives, a much more robust – but also considerably risky – design.

71% ownership

Wednesday’s deal will see OSE issue four million new shares in return for all of Effimune, with current OSE investors owning 71% of the merged entity.

Normally listed companies take advantage of strong share prices to use stock as an acquisition currency, but this is not the case here; OSE currently stands 25% below where it was at IPO. Nevertheless, Mr Peyroles points to the clinical and scientific rationale, “combining these two teams to create an immunotherapy player in Europe”.

Moreover, Effimune had only raised some €5m, so its private backers are making a paper profit on their investment. And the merged entity will not only benefit from a broader pipeline but should also be in a stronger position to raise more cash when the time comes.

Study Detail Tial ID
Atalante 1 Open-label, 500 A2-positive NSCLC pts, 2nd/3rd-line, vs chemo NCT02654587

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter

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