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Oxford BioMedica (OXB) has signed an out-licensing deal with Axovant for its Parkinson’s disease (PD) gene therapy AXO-Lenti-PD (previously OXB-102) worth up to $842.5m. Axovant plans to accelerate it rapidly into the clinic, with a Phase I/II dose escalation study in advanced PD patients to be initiated by year end. In addition to OXB’s numerous other partnerships, notably the recently signed Bioverativ deal and the ongoing collaboration with Novartis on its launched CAR-T Kymriah, this deal demonstrates OXB’s continuing world-leading status in lentiviral technology. We now include the Axovant deal in our model and value OXB at £614m.
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Oxford BioMedica |
Golden age for LentiVector as Axovant signs deal |
Corporate update |
Pharma & biotech |
8 June 2018 |
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Oxford BioMedica (OXB) has signed an out-licensing deal with Axovant for its Parkinson’s disease (PD) gene therapy AXO-Lenti-PD (previously OXB-102) worth up to $842.5m. Axovant plans to accelerate it rapidly into the clinic, with a Phase I/II dose escalation study in advanced PD patients to be initiated by year end. In addition to OXB’s numerous other partnerships, notably the recently signed Bioverativ deal and the ongoing collaboration with Novartis on its launched CAR-T Kymriah, this deal demonstrates OXB’s continuing world-leading status in lentiviral technology. We now include the Axovant deal in our model and value OXB at £614m.
Year end |
Revenue (£m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/16 |
27.8 |
(20.0) |
(29.35) |
0.0 |
N/A |
N/A |
12/17 |
37.6 |
(11.5) |
(14.14) |
0.0 |
N/A |
N/A |
12/18e |
72.6 |
4.5 |
9.88 |
0.0 |
92.5 |
N/A |
12/19e |
82.9 |
7.7 |
14.81 |
0.0 |
61.7 |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments. EPS updated for share consolidation.
Commercial revenue opportunity significant
The out-licensing deal for OXB’s AXO-Lenti-PD (previously OXB-102) adds to a growing and diversified revenue base. The deal includes $30m upfront ($5m as a prepayment for manufacturing-related activities), $55m in development milestones and $757.5m in commercial milestones in addition to tiered royalties of 7-10%. AXO-Lenti-PD is a re-engineered version of OXB’s gene therapy ProSavin, which was tested in a Phase I/II open-label study in 15 patients and demonstrated statistically significant improvements in motor behaviour. AXO-Lenti-PD has been engineered to increase dopamine production compared with ProSavin, which could lead to a more efficacious gene therapy product.
Lentiviral expertise continues to be recognised
OXB’s experience in providing commercial-grade LentiVector for Novartis’s Kymriah has validated both its technology and its manufacturing capabilities. This expertise continues to attract partners, as evidenced by the recent announcement of the Bioverativ collaboration to develop gene therapies for haemophilia patients (>$100m in milestones plus royalties). These partnerships and others continue to grow OXB’s revenues, driven in the near term by escalating sales of Kymriah. Furthermore, key inflection points from partnered assets OTL-101 (Orchard Therapeutics, BLA submission in H218) and CMB305 (Immune Design, Phase III clinical trial in synovial sarcoma initiation) could provide further inflection points.
Valuation: £614m or £9.35/share
Our increased valuation of OXB is £614m (£9.35/share) vs £513m previously. We now include the Axovant out-licensing deal in our valuation, but all other assumptions remain unchanged. We include the deals with Novartis, Bioverativ, Immune Design, Orchard Therapeutics and Sanofi, and OXB’s non-partnered assets OXB-201, OXB-202 (corneal graft rejection) and OXB-302 (cancer) in our valuation.
AXO-Lenti-PD: Sector primed for next-gen ProSavin
AXO-Lenti-PD is a lentiviral-based gene therapy, which aims to programme non-dopaminergic cells in the brain to produce dopamine that will correct levels that have declined due to Parkinson’s disease. Dopamine plays a critical role in movement and co-ordination and a reduction in its levels leads to the characteristic and progressive features of PD: tremor, slowness of movement and rigidity.
AXO-Lenti-PD is based on OXB’s first-generation gene therapy for PD patients, ProSavin (OXB-101). ProSavin was tested in an open-label Phase I/II trial, with most recent data published in 2014, which studied the long-term safety and tolerability of ProSavin. The trial tested 15 patients at three dose levels (low dose, 1·9 × 107 transducing units [TU]; mid-dose, 4·0 × 107 TU; high dose 1 × 108 TU). No serious adverse events were reported, with drug-related adverse events typically mild in nature, most commonly increased on-medication dyskinesias and on-off phenomena. A common measure of Parkinson’s patients is a comprehensive multi-question assessment of a patient’s motor and non-motor symptoms called the Unified Parkinson’s Disease Rating Scale (UPDRS). The scale is divided into multiple parts, a key component of which is part III, where a clinician evaluates a patient’s motor abilities (eg speech, hand movements, tremor at rest) with scoring from 0 to 4, where a score of 0 is normal and 4 signifies severe problems. Improvements in UPDRS-III after taking ProSavin were tracked over 48 months and can be seen in Exhibit 1.
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Exhibit 1: Mean UPDRS-III (OFF) score over time |
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Source: Oxford BioMedica |
While ProSavin demonstrated improvements in motor behaviour and a safe profile, further clinical trials were not undertaken, primarily because of funding limitations and a lower efficacy than could be achieved with standard, commercially available oral therapies (eg L-DOPA, a precursor of dopamine that can cross the blood-brain barrier). AXO-Lenti-PD (previously OXB-102) aims to address these shortfalls in efficacy by redesigning the genetic payload of the vector. Both ProSavin and AXO-Lenti-PD contain the same genes, but the specific ordering and stoichiometry of gene expression has been altered (Exhibit 2) to improve both dopamine and L-DOPA production levels. A core property of lentiviral vectors is their high gene capacity, which enables three genes to be inserted that express three critical enzymes (tyrosine hydroxylase [TH], cyclohydrolase 1 [CH1] and aromatic L-amino acid decarboxylase [AADC]) needed for dopamine synthesis.
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Exhibit 2: Differences between ProSavin and AXO-Lenti-PD |
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Source: Oxford BioMedica |
Axovant plans to initiate a Phase I/II trial by year end for advanced-stage Parkinson’s patients. This will consist of two parts. In the first part (A), patients will be tested across three dose levels with the lowest dose tested being the previous highest dose (1 × 108 TU) from the ProSavin trial. Once a dose has been selected, Part B of the study will be initiated. Additional patients will be enrolled into either the treatment arm or a sham arm (imitation surgical procedure). All patients will receive LentiVector via a one-time MRI-guided stereotactic delivery to the brain striatum. Endpoints have not yet been defined, but improvements in UPDRS scores and reduction of oral L-DOPA use are likely to be key.
We note that US-based gene therapy company, Voyager Therapeutics, has an AAV-based PD gene therapy in Phase I/II trials (VY-AADC). However, unlike AXO-Lenti-PD, which directly produces dopamine, VY-AADC has to be taken with oral L-DOPA, which is then converted into dopamine by the inserted enzymes. Clinical efficacy results have been mixed, but at the more optimal dosing of 900µl per putamen, encouraging efficacy data have been announced.
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