Humans may have an innate ability to fight off cancer and one of the world’s most prominent research centers, University of Texas MD Anderson Cancer Center, recently co-developed a novel regenerative therapy to tap into and actually harness this power to hopefully beat back certain forms of cancer. MD Anderson and Germany’s Affimed N.V., co-developers of a regenerative-based oncology therapy, recently announced that the first patient was successfully dosed with allogeneic cord blood-derived natural killer (cbNK) cells preloaded with the novel therapy AFM13. They have progressed to the AFM13 monotherapy phase of the treatment cycle. TrialSite breaks down the players and therapy associated with this first human study actually combining an NK cell product with an antibody whose primary mechanism is designed to specifically bind and activate NK cells and tumor cells in a bispecific manner. The study sponsors, MD Anderson and the National Cancer Institute, believe that this particular novel combination approach may in fact establish a basis for progressive cellular therapy combinations with Affimed’s ICE® constructs. This study is led by MD Anderson’s Yago L. Nieto.
The Problem & The Mission
Underlying this research is the concept of innate cell engagers. As it turns out, the immune system has two key components, including 1) the innate and 2) adaptive immune system, and they both act together to recognize and kill abnormal cells, such as tumor cells.
When an individual experiences the first initial stages of a cancer, there is a balance between the abnormally dividing cells and their immune response. The cancer, however, starts to disguise itself to trick the immune response—and hence evade detection.
The innate immune system supports the natural fight against cancer. They can be thought of as “first responders” to tumor cells, triggering “tumor-cell killing mechanisms.” The adaptive response provides additional support in identifying and helping to hunt down and kill tumors. One big problem: as cancer spreads in the individual patient, their innate immune cells don’t function properly.
Immuno-oncology-based therapies, designed to address this challenge and restore the protective nature of the patient’s immune system, still remain in their infancy. Most R&D in this field has focused on adaptive immune system activation. Enter Affimed, with their focus on R&D with the aim to overcome existing therapy limitations by restoring the immune systems’ innate ability to recognize and destroy tumor cells.
Who is Affimed?
Based in Germany and the U.S., Affimed (NASDAQ: AFMD) was founded two decades ago. The clinical-stage immuno-oncology company dedicates its research and development to finding ways for patients to get back their innate ability to fight cancer. Their “fit-for-purpose” ROCK® platform allows innate cell engagers to be designed for specific patient populations. The company is now developing single and combination therapies to treat hematologic and solid tumors. Most recently, they are now enrolling patients into a registration-directed study of AFM13 for CD30-positive relapsed/refractory peripheral T cell lymphoma and into a Phase 1/2 a dose escalation/expansion study of AFM24 for the treatment of advanced EGFR-expressing solid tumors.
What are Affimed ICE® Constructs?
Affimed designed and developed the ICE® products to help contribute to novel therapies, according to Dr. Andreas Harstrick, Chief Medical Officer at Affimed. In the company’s recent press release, he notes, “Engaging the innate immune system is a novel and promising therapeutic approach in oncology and our ICE products are designed to tap into this, which, thus far, has largely remained untapped in this field.” He continues, “Pre-loading innate immune cells with ICE takes this idea a step further and potentially intensifies the treatment’s effect, especially in patients who have an impaired immune system or low NK cell numbers.
Titled “Bispecific Antibody AFM13 Combined with NK Cells for Patients with Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas,” this Phase 1, investigator-initiated clinical trial (NCT04074746) is sponsored by MD Anderson in collaboration with the National Cancer Institute. An open-label, non-randomized, single-center, dose escalation trial evaluates the combination of AFM13 with cord blood-derived NK cells in adult patients with recurrent/refractory CD30-positive lymphomas.
The study sponsors seek to establish the safety and the recommended Phase 2 dose of AFM13-preloaded with cbNK cells, followed by weekly treatment with intravenous AFM13. Secondary objectives include assessing the overall, complete and partial response rates.
The sponsor’s hypothesis: combining immunotherapy with a monoclonal antibody-based investigational product, such as AFM13, can actually help the patient’s immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Hence, the sponsors will test whether giving the patient AFM13 loaded with NK cells along with AFM13 alone actually kills more cancer cells while depressing cancerous growth in those patients with CD30 positive AFM13-NK Hodgkin and Non-Hodgkin lymphomas.
Treating 30 patients, the study started in July, 2020 and runs through till April 15, 2023. The study is led by Principal Investigator Yago L. Nieto.
What is AFM13?
Affimed describes the therapy as a first-in-class CD30/CD16A ROCK-derived bispecific innate cell engager (ICE) that actually induces specific and selective killing of CD30-positive tumor cells by engaging and activating natural killer (NK) cells and macrophages, thereby leveraging the power of the innate immune system. As it turns out, AFM13 represents Affimed’s most advanced ICE clinical program, and its currently under study as a monotherapy in a registration-directed Phase 2 trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT)—NCT04101331.
Affimed Business & Financial Info
With a stock price at $3.65, Affimed’s market capitalization equals $286 million. Like most biotech’s, this one operates with losses and is funded by equity to keep pushing forward. Why does this company (and equity) have promise? Well, if you believe the company, its due to the following rationale:
· Focus: the company centers all attention on leading innate immune cell activation to treat cancer patients
· Strong leadership and sufficient capital till first half of 2022
· Promising pipeline & momentum: this includes 1) AFM13, interim data in PTCL as monotherapy; initiation of combination study with cbNNK cell product at MD Anderson and progression updates; 2) AFM24, dose escalation safety and activity data, initiation of dose cohort expansion as monotherapy and in combinations; 3) AFM28 & AFM32, initiation of IND-enabling studies of AFM28 and AFM32, IND filing of AFM28; 4) Genentech partnership.
The top 5 investors own about 36% of the company including NEA Management Company, LLC, Millennium Management, LLC, Blackrock, Inc., 683 Capital Management LLC, and Point72 Asset Management LP.
Investor Watch: Risks with Biotech
This particular venture, like most small biotech, is not for novice investors. Only accredited, well-informed investors should be involved with biotech. Affimed is working on a novel and exciting approach for those seeking cures to cancer. However, the risks remain the same. What follows are the standard risks associated with small biotech, and for that matter even larger pharma.
· Most small biotech show only a history of operating with financial losses
· The delay or even hold of clinical trials can be devastating on the small biotech. Studies can be delayed or held up for any number of reasons
· Reliance on contract manufacturers and contract research organizations limits control (and these entities have their own challenges)
· Most often lack of sufficient funding
· Dependence on just one or a couple of novel, investigational products
· Uncertainty as to the overall probability of regulatory approval
· Access to human capital/talent often constrained, limited
· Dependencies on partnerships or investors
Yago L. Nieto, PhD, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine