What is PTV insight?PTV insight is new publication from PharmaTelevision that provides insight and analysis of companies, technologies and individuals who have been featured on PharmaTelevision (PTV) plus additional views and information from the PTV team.

In this issue we focus exclusively on Targovax following a television interview with Magnus Jäderberg in Oxford, 2015.

October 2015

Fintan Walton Executive Producer, PharmaTelevision

Localised Immune ActivationThe key to widening the immuno-oncology approach in cancer?

Feature Interview

Norway based Targovax has recently combined with Oncos from Finland to bring together two key technologies that aim to take immunotherapeutic treatment of cancer to the next level. The new Targovax is combining its own peptide targeted immunotherapy with oncolytic immunotherapy technology from Oncos.

Speaking to PharmaTelevision, Magnus Jäderberg – CMO of Targovax, describes how the combination of these two technologies will advance the treatment of cancer beyond the recent major steps forward delivered by checkpoint inhibitors.

“We are bringing together two unique and complementary therapies in the field of immuno-oncology . . . and provide an opportunity for lesional immune activation.”

Whilst checkpoint inhibitors “take the brakes off the immune system” and provide general immune activation they do not generate local immune activation at the lesional level. Targovax technologies address this missing piece of the puzzle and provide two different approaches to local activation. This opens up highly interesting avenues for even more advanced immuno-therapeutic approaches to cancer. Indeed Targovax have evidence from clinical trials with chemo-refractive and tumour resected cancer patients that they can achieve

Targovax Feature Interview

Localised Immune ActivationThe key to widening the immuno-oncology approach in cancer?

immune activation both with their peptide approach when administered intra-dermally and with the oncolytic virus when injected directly into the tumour.

Taking checkpoint inhibitors to a new level

The discovery of checkpoint inhibitors, which liberate T-cells to detect and destroy cancer cells, has been the biggest breakthrough in cancer immunotherapy in recent years, leading to a rapid and unprecedented expansion in this area of the biotech industry. But, as Magnus Jäderberg explains, checkpoint inhibitors are only part of the story when it comes to stimulating the immune system to fight cancer:

“[despite] exciting developments in the checkpoint inhibitor area, which

“release the brakes” on the immune system leading to a generalised immune activation…what checkpoint inhibitors don’t do is activate at that lesion level.”

Whereas, clinical trials have demonstrated that targeted therapies can stimulate immune activation at the lesion level even without the use of checkpoint inhibitors, with significant implications:

“We’ve shown in the monotherapy study of ONCOS-102, in 12 late-stage solid cancer -all chemo refractory patients-, that 11 out of 12 patients actually had immune activation at the lesion level… We also saw in the same study with just the virus administered, a 40% stable disease right across the different solid tumours.”

Such positive results for stand-alone targeted therapies, naturally hint at the potential for combination treatments using checkpoint inhibitors alongside targeted immune-stimulating agents, an approach Targovax will explore:

“We don’t need a checkpoint inhibitor, but the way we’re going to develop the compound is to combine with checkpoint inhibitors, and standard-of-care chemotherapy in different indications . . . We now know that the combination of local immune activation with a checkpoint inhibitor has potentially a very interesting future.”

Targovax’ lead product, TG01, is a 7-peptide intra-dermal immunotherapy which causes immune activation at a localised level, while Oncos’ lead product, ONCOS-102 is an engineered oncolytic virus armed with immune-stimulating transgenes injected directly into solid tumours. TG01 and ONCOS-102 cause local immune activation by different but potentially complementary mechanisms, and both are at the cutting edge of cancer therapeutic vaccines.

Magnus Jäderberg, CMO of Targovax, talks with Adrian Dawkes, VP, PharmaVentures.

Feature Interview Targovax

Unique approaches addressing RAS mutations

Cancer vaccines have not delivered on their early promise and have failed to provide efficacious treatments for several cancers despite high levels of investment in the area. One of the most encouraging aspects of Targovax’ programme is that its peptide immunotherapy specifically addresses solid tumours characterised by RAS mutations, an area of urgent medical need. As Magnus Jäderberg explains:

“20-30% of solid tumours have RAS mutations… [our] peptide vaccine is unique in the sense that we are the only ones who have developed a RAS mutation specific vaccine.”

Targovax is well advanced in the clinic with both peptide and virus approaches. TG01 is currently half way through a phase II study in resected pancreatic cancer (the phase I study demonstrated immune responses in all patients, with no substantial toxicity observed), and ONCOS-102 has successfully completed Phase I clinical studies in chemo-refractive patients with confirmed tumor-specific and systemic activity. ONCOS-102 will enter further clinical studies in the near future, for the treatment of solid tumours such as melanoma, malignant pleural mesothelioma, and ovarian cancer. With Targovax’ TG01 already showing good results in resected pancreatic cancer, and another follow-up therapy, TG02, in development going into colorectal cancer next year, advances in these areas looks encouraging. The technologies potentially have wide application across several types of cancer and Targovax is

not just focusing on niche areas of high unmet need but also intend to use their approach to treat many of the more common cancers.

What are Targovax’ future opportunities?

The major players in cancer therapeutics are currently very focused on immune checkpoint inhibitors and the benefits they can bring. Targovax have taken an intelligent approach by understanding the limitations of checkpoint inhibitors and bringing together technologies to address the gaps. Targovax’ localised lesional immune activation could be as important as checkpoint inhibitors in the continued fight against cancer. Just as we have seen an explosion of collaborations and deals in the checkpoint inhibitor space, we may be about to see a second wave with Targovax on the crest.

“We’re excited because after we released our first set of data at CIMT in 2014, we had interest from both academic centres, including high profile immuno-oncology centres. We also had approaches from big pharma, especially from the checkpoint inhibitor side, and that’s interesting because the checkpoint inhibitor companies realise the need to combine with other immuno- oncology compounds . . . Lesional immune activation is an attractive target for combination work.”

The strategy behind the Targovax-Oncos merger is indicative of massive advances in the area of Cancer therapeutics, with the increasing focus on facilitating the body’s own immune system to fight cancer. What sets Targovax apart in a rapidly burgeoning industry, is bringing two unique and complementary therapies together at the cutting edge of immuno-oncology. As we know, the road of progress is littered with vaccine technologies that haven’t made the cut, but when asked why Targovax will succeed where previous biotech companies have failed, Magnus Jäderberg is clear:

“The key success of any immune oncology compound is to be able to show immune activation at the local, lesional, level, and if you look back over time, all of those peptide vaccines that haven’t made it don’t have that local, lesional, immune activation . . . that’s what we have for both vaccines in our development programme, and I think that’s the key thing in order to predict a positive clinical outcome.”

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Targovax has two unique and complementary technologies

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Source: Ranki et al., OncoImmunology 2014; Vassilev et al., OncoImmunology (accepted 2015)

THE TARGOVAX OPPORTUNITY AND PORTFOLIO

Activating the immune systemTeaching the system to

recognise cancer as a threatMobilising T-cells to attack

cancer cells

1 2 3

Injection:The virus is injected, starts to replicate and lysis the cells

unique tumor antigens are released Response:

The immune system learns to recognize the unique cancer cells of each patient

Result:T-cells kill the cancer

RAS mutation specific T cell receptor

Response:The immune system learns to recognize the RAS mutations

Injection:The peptides are injected into the skin together with an adjuvant

Lymph nodeONCOS-102

TG01Result:T-cells kill the cancer

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…this provides the rationale behind ONCOS-102

2

THE TARGOVAX OPPORTUNITY AND PORTF

ONCOS-102 has shown to increase tumor infiltrating CD8+ T-cells in 11 of 12 patientswith late stage treatment resistant cancers

Source: Internal data on file

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100

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FI1-

18FI

1-02

FI1-

15FI

1-08

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1-09

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14FI

1-19

4 patients showed >10 fold increase

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7 patients showed 1.5 to 8 fold increase

1 patient showed no increase in CD8 post treatment

Baseline After ONCOS-102

FI1-17

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FI1-14

FI1-19

ONCOS-102 TG01

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