Event – Innate's value will be clearer by year end

Innate Pharma yesterday confirmed itself as an independent immuno-oncology player to watch, with the release of encouraging early-stage data on its remaining non-partnered, clinical-stage asset.

The news helps set the stage for even more important presentations due before year end, with three trials expected to yield important signals on its two partnered projects. With a market value of €607m ($662m) the French biotech has a relatively modest valuation compared with US peers in the same space. This gap could narrow if strong evidence of utility emerges.

Company   Innate Pharma
Projects Monalizumab
Lirilumab
Market cap   $662m
Product NPV   Monalizumab $343m
Lirilumab $335m
% of market cap Monalizumab 52%
Lirilumab 50%
Event type Phase II data
Date   Q4'16

The data released yesterday concerned IPH4102, an anti-KIR3DL2 antibody that Innate describes as first in class. The project aims to destroy cutaneous T-cell lymphoma (CTCL) cancer cells – KIR3DL2 is an inhibitory receptor of the KIR family that is expressed in all subtypes of CTCL. After binding to the tumour cell the agent recruits and activates a patient’s natural killer (NK) cells, part of the innate immune system that the company exploits with much of its pipeline.

An ongoing open-label, phase I trial is seeking to recruit refractory or relapsed patients across Europe and the US – 25 to 40 will be enrolled into a dose-escalation phase testing 10 dose levels. A subsequent cohort expansion will select 10 patients in two CTCL subtypes, who will be dosed until progression.

In a poster at the Third World Congress of Cutaneous Lymphomas yesterday, data from the first seven doses administered was presented, in 16 patients. Of these, 13 have Sézary syndrome and two mycosis fungoides, CTCL subsets with high unmet need and poor prognosis and which will represent the expanded cohorts in the second phase of the study.

No dose-limiting toxicity was seen, with an overall response rate of 38%, Innate said. The reaction from the sellside was widely positive, with analysts commenting on what seems to be an emerging dose response.

Analysts at Bryan Garnier were impressed enough to start attributing a value to the asset, noting that the efficacy seems to compare favourably to other promising drugs in this area. Duration of response will be something to watch, however, they added. The first phase of the study will be completed by the second quarter of 2017.

Mounting evidence

Of course the main caveat to these data is its very early stage, and more robust readouts are still needed. Indeed this caution should be applied to Innate's other clinical assets, none of which has generated substantial evidence to date.

This could start to change by the end of the year for lirilumab, Innate’s Bristol-Myers Squibb-partnered anti-KIR antibody.

At the Society for Immunotherapy of Cancer on November 12 preliminary efficacy data will be presented on lirilumab in combination with Opdivo. The phase I/2 study is again a cohort expansion study – the cohort presented will be patients with squamous cell carcinoma of the head and neck (SCCHN). Data from Keytruda and Opdivo in this setting, in the table below, have set the bar here.

Leerink analysts believe that the combination with Opdivo in solid tumours represents the biggest opportunity for the asset, but caution that very little evidence has been demonstrated to date in this setting, for lirilumab or indeed the anti-KIR mechanism. Still, the presentation has made it into the conference as a late-breaking abstract, so many are hoping for a compelling message to emerge.

Innate's clinical pipeline
Project Trial ID Details Data to watch
Phase II
Lirilumab NCT01714739 Opdivo combo in H&N Keytruda, granted accelerated approval on ORR 16%, CR 5%
Opdivo - ORR 13.3%, OS 7.5 mths vs 5.1 in Checkmate-141
NCT01687387 Effikir Trial is powered at 80%, based on median leukaemia free survival of 12 mths in placebo vs 20 mths in liri' group
NCT02252263 Empliciti combo in MM Eloquent-2 trial: Elo + Revlimid + dex PFS 19.4 mths, ORR 79%, vs Rev + dex PFS 14.9 mths, ORR 66%
Monalizumab NCT02459301 Gynaecologic malignancies -
Phase I
IPH4102 NCT02593045 CTCL Alcanza trial w/Adcetris in CD30+: ORR4 56% vs 13% (Data at Ash)
Poteligeo (mogamulizumab) ORR 38% (Japan approval only, US PIII ongoing)

Another pending lirilumab trial, which some believe will feature at Ash in December, tests the antibody in combination with Empliciti (elotuzumab) in multiple myeloma. The hope is that lirilumab will enhance the efficacy of the anti-SLAMF7 antibody, which is currently only approved in combination with Revlimid and dexamethasone.

Harder to predict timing-wise is data from the Effikir trial, a single-agent maintenance study of lirilumab in elderly acute myeloid leukaemia patients (Upcoming events – Testing lirilumab in leukaemia and pridopidine in Huntington’s, July 21, 2016).

Effikir has for some time been considered the trial to watch for lirilumab. However, with combination immuno-oncology strategies being considered ever more important, its outcome is perhaps less pivotal that it once was for Innate. That is not to say that failure or even a disappointing show of efficacy will be taken badly, as a strong read out could pave the way for accelerated EU approval.

Elsewhere in Innate’s pipeline, data on Astrazeneca-partnered monalizumab will emerge at the EORTC-NCI-AACR molecular targets symposium. Preliminary data will feature at a poster session on November 30th from a dose-ranging, single agent study in patients with gynaecologic cancers.

As such, with so much news on the horizon for Innate before year end, a better consideration of the company’s value will soon be possible. On the surface, given its status as an early-stage European biotech company, this would already seem to be rich.

However, this is the world of immuno-oncology, where "normal" valuations no longer seem to apply.

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @ByAmyBrown on Twitter

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