While Nektar Therapeutics set the SITC meeting alight this week, showing that immunotherapy might work in initially “cold” tumours, Oncosec enjoyed an even steeper jump – albeit from a much lower base – on data that conceptually were rather similar.
The similarity lies in both groups’ attempts to turn tumours immunogenic, thus making them amenable to treatment with checkpoint blockade. But one reason for caution, and perhaps for the fact that even including last week’s 60% jump Oncosec is worth just $70m, is that there is little about the company’s approach that seems unique, and competition could be swift (see table below).
This is not to deny that the data Oncosec reported at the SITC meeting last week were impressive. But of course all the group is fundamentally doing is priming tumour cells with the cytokine IL-12, which has pro-inflammatory effects, before hitting the cancer with checkpoint blockade, which is known to work best in immunogenic or “hot” tumours.
And of course there is nothing proprietary about IL-12 itself. At best Oncosec can hope that the method by which it delivers this cytokine – electroporation – offers some kind of unique advantage, though it has to be noted that electroporation itself is a widely used scientific procedure for getting large proteins or genetic matter through the cell membrane and into cells.
Oncosec insists that its particular electroporation system is proprietary and patent protected. The company could also argue that, having presented positive data at SITC, it holds a strong first-mover advantage.
Unlikely to respond
Its study concerned IL-12 delivered via its Immunopulse device, combined with Merck & Co’s Keytruda, specifically in metastatic melanoma that had been deemed unlikely to respond to anti-PD-1 therapy.
Clearly, much depends on how predicted non-responders are identified. Lending strong support was the fact that one complete responder had already failed on Keytruda (another had been on Amgen’s T-Vec), and that two patients progressing on Yervoy, and on Yervoy, Keytruda and Opdivo, went into partial remission.
Overall, in the 22 subjects taking part in this trial, there were 11 remissions; in the total population there had been 10 anti-PD-1 and seven anti-CTLA4 failures, and Oncosec said none of the 11 responders had relapsed, with the two most advanced around 26 months out.
A separate issue, identified some years ago in early work that led to the development of Immunopulse IL-12, is that this approach requires lesions to be accessible to the electroporator device; only subjects with such lesions were recruited into the Keytruda combo study.
The positive data are all very well, but even if results in a handful of subjects hold water, and if Oncosec’s definition of predicted PD-1 non-response is accepted, the issue of market exclusivity looms large.
Oncosec's stock exchange filings accept that intellectual property the company has licensed might not provide sufficient rights or prevent competitors from pursuing similar technology.
A quick perusal of the Clinicaltrials.gov database reveals several trials combining IL-12 delivery with various therapeutic approaches, including with Keytruda using recombinant IL-12, and with Merck KGaA/Pfizer’s Bavencio.
Others include IL-12 gene therapies and Ziopharm’s Rheoswitch-controlled Ad-RTS-hIL-12. Of course not all of these will be commercial threats to Oncosec, but if the IL-12 plus anti-PD-(L)1 approach is as promising as it looks Oncosec might not have the market to itself.
|Selected anticancer approaches delivering IL-12|
|IL-12 treatment||Sponsor||Combo therapy||Indication||Trial ID|
|Immunopulse IL-12||Oncosec||Keytruda||Melanoma predicted to be PD-1 non-responsive||NCT03132675|
|Recombinant IL-12||NCI||Keytruda||Solid tumours||NCT03030378|
|M9241 (NHS-IL12)||Merck KGaA||Bavencio||Advanced solid tumours||NCT02994953|
|Recombinant IL-12||NCI||Erbitux||Head and neck squamous cell carcinoma||NCT01468896|
|GEN-1 (IL-12 gene therapy)||Celsion||Pegylated doxorubicin||Ovarian cancer||NCT01489371|
|GEN-1 (IL-12 gene therapy)||Celsion||Chemotherapy||Ovarian cancer||NCT02480374|
|IL-12 gene therapy||Henry Ford Health System||Chemotherapy||Metastatic pancreatic cancer||NCT03281382|
|Hemamax (recombinant IL-12)||Neumedicines||Skin electron beam therapy||Lymphoma||NCT02542124|
|INO-9012 (electroporated IL-12 )||Inovio*||INO-1400||High-risk solid tumours||NCT02960594|
|Ad-RTS-hIL-12||Ziopharm||Veledimex (activator ligand)||Paediatric brain tumour||NCT03330197|
|Ad-RTS-hIL-12||Ziopharm||Veledimex (activator ligand)||Glioblastoma or malignant glioma||NCT02026271|
|Note: *Inovio has licensed IP to Oncosec.|