I know how critical it is to be measured when setting expectations. In business, as in life, none of us aspire to overpromise and under-deliver.

Indeed, as any business venture must do when communicating with investors and the public, we at Affimed are careful to use so-called “forward-looking statements” in laying out business goals. For example, when we report on successful results — as we did in April, after initial data from an ongoing clinical trial showed a 100% response rate to Affimed’s approach to activating the innate immune responses in patients with advanced blood cancer — we include a disclaimer to qualify statements that include terms such as “anticipate,” “believe,” “intend” and “predict” and distinguish them from “statements of historical fact.”

Although it is necessary to attenuate these kinds of forward-looking statements, the imperative to innovate demands that leaders internalize them, believe in them and make them a shared mindset for imagining — and pursuing — what is possible.

Believing in the possible

The initial results we reported in April are a testament to the power of imagining and believing in new possibilities — in this case, the potential to restore patients’ innate ability to fight cancer.

Led by the University of Texas MD Anderson Cancer Center, the investigator-sponsored Phase 1 trial is studying the safety and efficacy of combining AFM13, Affimed’s first-in-class innate cell engager (ICE), with cord blood-derived allogeneic natural killer (NK) cells to patients with recurrent or refractory CD30-positive lymphomas. In this ongoing trial, the first four patients, all heavily pretreated and exhausting all treatment options, showed significant disease reduction with an objective response rate of 100% — two complete responses and two partial responses — and none observed incidences of cytokine release syndrome, neurotoxicity syndrome or graft-versus-host disease. An especially poignant outcome: one of the responsive patients had been advised to enter hospice care prior to participating in the trial.

The results validated and affirmed our conviction that the innate immune system can eliminate cancers — a view that the field of immuno-oncology had largely underestimated.

Apart from academic research into the innate immune system, companies over the past 10 years primarily focused on the adaptive immune system. This is because engaging adaptive immune cells such as T cells to fight tumors historically promised greater efficacy than engaging innate cells like NK cells and macrophages. Even though engaging T cells poses a risk of toxic — even deadly — side effects for patients, the view was that it was the only way to generate an efficacious immune response.

Our strategy was grounded in the possibility of increasing the efficacy of the innate immunity approach. We followed the biology — and the biology showed us not only that the efficacy of innate cell engagement doubled when applied to lymphoma patients with certain indications, but that a strong activation of innate immunity can induce a strong activation of adaptive immunity. And it appears to be much safer than T cell-directed products.

Validating the possible

We pursued innate cell engagement for many years and had early data supporting its promise, and our validation came in 2018 in the form of a pivotal collaboration with Genentech, the world’s largest developer of oncology medicines and the leader in developing therapeutic antibodies. Given its pioneering leadership in the field of biotechnology, the conventional wisdom within the industry was that Genentech would own and be able to manage every antibody-related bispecific technology. But they recognized the advantage of collaborating with Affimed and leveraging our understanding of innate activation, our clinical data and our own considerable intellectual property. Since then, our approach continues to receive further validation. We have added more meaningful strategic collaborations to bolster and advance our clinical efforts, including with Merck, Roche and Roivant.

Expanding the possible

Our collaboration with Genentech positioned Affimed to further explore innate immunity — and expand a sense of its possibilities — through the clinical trial with MD Anderson.

Prior to partnering on the trial, MD Anderson had found that it was possible to introduce donor-derived NK cells into patients without rejection. While the treatment did not prove to be highly efficacious, it demonstrated that patients could safely be given a novel immune system, setting the stage for us to test the efficacy of combining donor-derived NK cells with Affimed’s ICE.

Together with MD Anderson, we developed the idea of pre-complexing NK cells by combining them with ICE. In effect, this reengineers the NK cells to recognize and bind with tumor cells. In early preclinical applications, the combination caused high response rates.

There has been a considerable effort by other companies developing cellular NK cell products. However, they have been realizing that it requires targeting of the NK cells to attack the tumor. The generation of ICE pre-complexed NK cells turns out to be simple, as it does not require any sophisticated and cumbersome engineering.

As the MD Anderson trial continues to generate data from additional patients, Affimed is now fully engaged with a substantial pipeline for developing new biotechnologies and immuno-oncological applications, including new ICE focused on recognizing and eliminating further heme malignancies and even solid tumors. Having built such a broad pipeline, our approach can address many major cancers. This means there really is no limit to the possibilities we might explore — or the forward-looking statements we might make — in the years to come.

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