In today’s Sunday Interview we talk to Carlos de Sousa, CEO of Immunicum. He shares his thoughts on why lead drug candidate ilixadencel may be the next generation of immuno-oncology therapies, on negotiating with two of the world’s biggest pharma companies and on what made some of Sweden’s top institutional investors, including hedge fund giant Max Mitteregger, commit to investing 178 million SEK in the company. 

Carlos de Sousa, vd Immunicum

Carlos de Sousa, vd Immunicum.

Carlos de Sousa, Immunicum is developing ilixadencel, a cell-based immunotherapy designed to activate or boost the immune system of cancer patients to kill tumor cells. What are the key advantages of your drug concept?

– We have quite a unique approach and we see several expected advantages with ilixadencel: injecting ilixadencel directly into a tumor brings the patient’s own immune cells, including natural killer (NK) cells and dendritic cells, to the tumor which leads to an increased immune reaction. The immune reaction attacks the cancer cells resulting in the release of neoantigens that are used to activate/prime tumor-specific cytotoxic (killer) T cells. Ideally this will also increase the effectiveness of the other components of combination therapy.

– Ilixadencel is applicable for the majority of solid tumors. In addition, Ilixadencel is an off-the-shelf cell-based therapy which can be produced on a larger scale and is ready to be administered when needed.

Immuno-oncology is basically the hottest area in medicine right now and the top pharma companies are all competing to be at the forefront of the development of new molecules, antibodies, checkpoint inhibitors and combinations thereof. Where would you say that Immunicum is positioned in this global competitive landscape right now?

– We have seen the initial wave and excitement of checkpoint inhibitors (CPIs) being introduced as the first effective immunotherapies in oncology. The second wave consisted of checkpoint inhibitors being introduced into first-line treatment as combination with targeted therapies and chemotherapies.

»We believe ilixadencel’s position as a potential backbone therapy to both targeted therapies and checkpoint inhibitors can take the center stage.« – Carlos de Sousa, CEO Immunicum

– Now, top pharma companies will be looking at the next wave of combinations of immunotherapies, in which ilixadencel is strongly positioned with a highly complementary mechanism of action, excellent safety profile and advanced stage of development, with over 90 patients already treated. We believe ilixadencel’s position as a potential backbone therapy to both targeted therapies and checkpoint inhibitors can take the center stage as the Phase II MERECA and Phase Ib/II ILIAD studies start reading out in 2019 and onwards.

And where do you see the company in 3 years?

– Our goal is to explore the potential of ilixadencel in a range of indications and accelerate its development towards regulatory approval to help patients with solid tumors as quickly as possible. We are now initiating manufacturing activities that will ensure commercial scale manufacturing to enable these goals. In three years, we will have made significant progress in manufacturing and clinical development and expect pivotal studies to be initiated on our path to the market, potentially in collaboration with a top pharma company.

The Nobel Prize was recently awarded for groundbreaking advances in using immunotherapy for the treatment of cancer and billions of dollars being are invested in thousands of research projects around the world. Within the industry, a lot of focus is directed towards combination treatment regimens. What does this mean for Immunicum?

– As most types of cancer continue to remain notoriously stealthy and difficult-to-treat, the next wave of innovation is currently being led by novel combination therapy approaches that attack the cancer from multiple angles. This approach was recognized by the 2018 Nobel Prize in Medicine which was awarded to two cancer immunotherapy researchers for their studies in determining how to unleash the body’s immune defenses against cancer, which has resulted in new therapies such as checkpoint inhibitors (CPIs).  The most stunning effects in patients have been with combining standard of care with CPIs to provide a more diverse and effective array of treatment options for patients.

– Similarly, Immunicum’s treatment is centralized on the idea of strengthening the ability of the patient’s immune system to recognize and kill tumor cells. Combined with checkpoint inhibitors, this already has the possibility to make a real difference in patients with solid tumors. We will also continue to study different combination approaches in preclinical studies to gain further insight on the most advantageous combinations. As ilixadencel has an excellent safety profile and is given in only 2 or 3 injections, it can become a crucial add-on to existing combination regimens that may already be limited due to their safety burden on patients.

»We are continuously in touch with Big Pharma to update them on our progress and explore collaboration opportunities.«

You recently announced Immunicum’s first Big Pharma collaboration agreement. Pfizer and Merck Germany will supply the checkpoint inhibitor avelumab, to be evaluated in combination with ilixadencel in a clinical Phase II study in patients with head and neck cancer, as well as gastric cancer. How did you feel when the contract was signed and for how long were you in dialogue before the collaboration was decided upon?

– We were delighted when the contract was signed as this collaboration is a form of external validation by the industry and will allow us to expand the Phase Ib/II ILIAD study into Europe in addition to the USA. It continues to support us in our pursuit of establishing ilixadencel’s potential as a backbone component of various combination treatments. We are continuously in touch with Big Pharma to update them on our progress and explore collaboration opportunities. It is always hard to say when initial discussions and introductory meetings with potential partners become negotiations, but our dialogue with Pfizer and Merck KGaA has been going on for more than a year.

Have you experienced any increase in attention from an industry perspective after the agreement was announced – and will this collaboration open any new doors for Immunicum?

– We are very pleased with the announcement and see it as one accomplishment from our ongoing efforts to build Immunicum’s network within the global industry among not only potential partners and collaborators, but also clinicians and Key Opinion Leaders whose acknowledgment of the opportunity ilixadencel presents is also important. As we continue to present Immunicum to different audiences, we expect an increase in attention.

Obviously, landing a deal with two major global pharma companies is an important validation of Immunicum’s concept and the potential of ilixadencel as a possible combination compound to treat cancer. What will be the financial implications for Immunicum if the study is a success?

– The focus of this agreement was on providing access to this ground-breaking class of therapies and solidifying our ongoing dialogue with these two companies. There are no financials relating to the collaboration agreement, but if the study is successful and renders positive results, it will undoubtedly establish ilixadencel as a promising part of combination therapies. We will be combining ilixadencel with different checkpoint inhibitors, as recommended by regulatory authorities, and will therefore not be solely dependent on a collaboration with one partner if we are successful. As we maintain full rights to ilixadencel, we have complete flexibility to enter into the most valuable partnerships if the study is a success.

»As we maintain full rights to ilixadencel, we have complete flexibility to enter into the most valuable partnerships if the study is a success.«

Recently, your new partners were forced to announce negative results from a phase III study in which avelumab was combined with chemotherapy for treatment of ovarian cancer. Is that something that worries you, in regards to your own upcoming combination trial with avelumab?

– Avelumab is already approved and marketed as a drug and therefore has shown efficacy in a number of indications in line with other checkpoint inhibitors. It is also currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including eight Phase III trials, and more than 9,000 patients across more than 15 different tumor types. In this way, it is exploring the most efficacious combinations for a range of indications.

»The results of the recent trials, including studies from other pharma companies, emphasize the challenges still in place and the need for next-generation immunotherapy combinations, such as ilixadencel.«

– In the case of the advanced ovarian cancer trial, the failure may have been a result of various factors including the extreme severity of this type of cancer as well as the advanced disease state of the patients. Regardless, we do not see any concerns for the combination study with avelumab and ilixadencel and believe that the results of the recent trials, including studies from other pharma companies, emphasize the challenges still in place and the need for next-generation immunotherapy combinations, such as ilixadencel.

Can you describe the time frames for the study – when will it start and when will you have data to present?

– We expect the first patient for the multi-indication study to be enrolled before the end of 2018. Following successful enrollment and trial initiation, we will be able to provide an update on the expected progress of the trial for 2019.

You are currently in the process of a rights issue and a directed share issue which will raise a total sum of 351 million SEK. Why are you raising that much capital at this point?

– In order to increase the value of ilixadencel we need to invest in its development. The Phase Ib/II study ILIAD has been expanded to include 21 patients in the Phase Ib part of the study and will start in the US before the end of 2018. In addition, we need to secure full scale production of ilixadencel so that we are ready to manufacture it at commercial scale for pivotal studies and potential commercial launch. This demands large investments in scaling up manufacturing and process development. If we don’t make these investments now, we will face delays later on which will decrease the potential commercial value of ilixadencel. Every month in which we can focus on implementing and meeting development and manufacturing goals will increase the value and accelerate the time to market of ilixadencel.

»In order to increase the value of ilixadencel we need to invest in its development. «

– We will also conduct supportive preclinical studies to continue to explore promising treatment combinations and further strengthen the preclinical data package.

– The fact that we will be financed towards the end of 2021, provides us with the financial stability to focus on reaching several important value inflection points during this period.

No less than 178 million SEK will be raised by anchor investors such as the Second and the Fourth AP fund, Max Mitteregger’s fund Gladiator, Alfred Berg, Nordic Cross and Adrigo. What do these major investors see in Immunicum’s future that made them commit at this relatively early stage of clinical development?

– The company has reached several important milestones during 2018. We completed the recruitment of patients for the Phase II MERECA trial and the Phase I/II GIST trial and we received approval from the FDA for the Phase Ib/II ILIAD clinical trial protocol, in which ilixadencel will be combined with checkpoints inhibitors. Furthermore, Immunicum completed the move to the Nasdaq Stockholm main market at the beginning of the year.

»Our focus is on successfully developing ilixadencel which will drive value for the company and our shareholders by demonstrating the therapeutic value of the approach.«

– These achievements, together with the prospects of reaching important value inflection points in the not too distant future, have been instrumental in our efforts to gain attention from institutional investors. We are delighted that the Second and Fourth Swedish National Pension Funds, Gladiator, Nordic Cross and Alfred Berg, among others, have agreed to participate in a Directed Issue. Their commitment is a clear acknowledgment of Immunicum’s attractiveness as an investment, and both the new investors as well as Immunicum management believe that this is indeed a good opportunity and timing for a parallel Rights Issue which allows participation by our current shareholders under the same conditions.

Immunicum has a portfolio with a number of clinical phase and soon-to-be clinical phase projects in development. Which major milestones are you looking forward to achieving in the near future, say in 12-18 months?

– Our primary focus is initiating the multi-indication ILIAD study and providing updates on the progress from that trial. We also highly anticipate announcing top-line results on survival from the Phase II MERECA study in the third quarter of 2019.

The I/O field has seen quite a few major license deals and acquisitions this year – you actually mention a few in your prospectus, such as the BMS-Nektar deal of 1,85Bn USD and Janssen’s acquisition of BeneVir at 1 billion USD. Do you expect a future license deal for Immunicum in those numbers as well, given that you are able to show positive data in your ongoing trials?

– Our focus is on successfully developing ilixadencel which will drive value for the company and our shareholders by demonstrating the therapeutic value of the approach. If we are successful in doing that, there are numerous corporate opportunities for the company, but we cannot anticipate now, and cannot be dependent on, the potential outcome of partnering discussions. The likelihood and size of a licensing deal is further dependent on market trends and other external factors not in our control.

Final question, what will happen right now at Immunicum, and for the remainder of 2018?

– We are focused on concluding the current capital raise and also anticipate enrolling the first patient in the multi-indication ILIAD study by the end of 2018.

 

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