In an interview with PharmaShots, Dr. Andreas Harstrick, Chief Medical Officer at Affimed shared his views on updated clinical data related to their lead innate cell engager AFM13 at the virtual 62nd American Society of Hematology (ASH) annual meeting.

Shots:

• The study showed an ORR of 42% (6/14 patients) and demonstrated clinical activity in two out of four patients with failure of brentuximab vedotin (Adcetris)
• Affimed's ROCK platform is based on the scientific approach of leveraging a patient's innate immune system in the fight against cancer, which has remained largely untapped as a therapeutic approach in oncology
• AFM13 is the first-in-class tetravalent, bispecific innate cell engager that works by binding to CD30 on tumor cells and to CD16A on innate immune cells engaging the patient's immune system in fighting cancer through NK cells and macrophages

Tuba: Can you put some light on clinical data of Phase 1b/2a study in patients with CD30-expressing lymphoma with cutaneous involvement?

Andreas: We were pleased that the results of Phase 1b/2a study of our innate cell engager (ICE) AFM13 as a monotherapy in patients with relapsed or refractory CD30-positive lymphoma with cutaneous involvement have been presented at this year's American Society of Hematology virtual meeting. The study showed an objective response rate of 42 percent (6/14 patients) and demonstrated clinical activity in two out of four patients with failure of brentuximab vedotin (Adcetris).

We are excited about the results of this study, as the data suggest that AFM13 initiates NK cell tumor infiltration and recruits and engages NK cells for tumor cell killing. AFM13 was well tolerated and showed a promising objective response rate in patients with a high therapeutic need.

Tuba: Discuss the importance of NK cells in achieving the anti-tumor responses?

Andreas: Natural killer cells are powerful innate immune cells that are a part of the body's first line of defense and have the ability to trigger a complete immune response. However, in cancer patients, NK cells can become compromised, or tumor cells may escape their recognition.

Utilizing our Redirected Optimized Cell Killing (ROCK) platform, we develop tetravalent, bispecific ICE molecules that possess strong cell-retention binding to NK cells and macrophages and effectively direct these innate immune cells to the tumor target to kill cancer. Combining our ICE molecules with adoptive NK cell transfer is currently under investigation in a Phase 1 trial and aims to ensure that patients have sufficient active NK cells to be directed to the tumor and induce tumor cell killing.  

Tuba: What is the mechanism of action of AFM13?

Andreas: AFM13, our lead, late-stage ICE molecule, represents a new approach of activating the innate immune system in the fight against CD30-positive lymphoma. AFM13 redirects NK cells and macrophages to tumor cells by binding to CD16A on innate immune cells and CD30 on cancer cells. The innate immune cells then kill the tumor cell through Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) or Antibody-Dependent Cellular Phagocytosis (ADCP).

Tuba: Can you summarize the presentation & abstracts presented at ASH in a non-scientific way?

Andreas: We were honored that data around our lead ICE molecule, AFM13, were presented this year at the American Society of Hematology virtual annual meeting. We were particularly excited about the Phase 1a/2b data which analyzed the safety and efficacy of AFM13 in patients with CD30-positive lymphoma who were heavily pretreated and were relapsed or refractory to prior therapies.

The study revealed that AFM13 as monotherapy was well tolerated and demonstrated a promising objective response rate, with 42 percent of patients showing either a partial or complete response.

Tuba: Can we have a glance at your ROCK platform?

Source: Affimed

Andreas: Affimed's ROCK platform is based on the scientific approach of leveraging a patient's innate immune system in the fight against cancer, which has remained largely untapped as a therapeutic approach in oncology.

Our ROCK platform is the most clinically advanced technology platform for developing innate immunity therapies. By leveraging a CD16A-binding epitope, our platform is able to generate ICE molecules that mimic the natural way the human body employs the innate immune system to effectively fight cancer. The modular nature of the platform also allows for the tailoring of ICE molecules for new therapeutic indications.

The ROCK platform is the foundation of our growth strategy because of its ability to generate a plethora of diverse ICE molecules for a multitude of hematologic and solid tumor cancers with consistent profiles in tumor lysis and safety.

Tuba: What are the different indications in which Affimed is evaluating AFM13?

Andreas: We are currently evaluating AFM13 as a monotherapy for the treatment of CD30-positive lymphoma, including Hodgkin lymphoma, peripheral T cell lymphoma and transformed mycosis fungoides. Additionally, AFM13 is being assessed as combination therapy with adoptive NK cells or a checkpoint inhibitor in CD30-positive lymphoma and Hodgkin lymphoma, respectively.

We were honored to announce that the results of the Phase 1 combination study with AFM13 and Merck's KEYTRUDA (pembrolizumab) were published in the esteemed Blood journal last month. The study showed a complete response (CR) rate of 46 percent and an objective response rate (ORR) of 88 percent in patients with relapsed or refractory Hodgkin lymphoma. As a monotherapy, KEYTRUDA demonstrated an ORR of 69% and a CR of 22.4% in the KEYNOTE-087 trial. These data support the scientific rationale for combining innate cell engagers with checkpoint inhibitors.

Tuba: Please showcase Affimed's diverse clinical pipeline of innate cell engagers designed to activate innate immunity?

Andreas: Our ROCKplatform was created to generate diverse, CD16A-targeting ICE molecules, which can be customized for a variety of specific tumor targets. Our broad clinical pipeline is comprised of a number of wholly-owned programs, as well as a number of out-licensed programs.

AFM13 is our lead candidate, targeting CD30 and is in development for CD30-positive lymphomas. A registration-directed Phase 2 study in peripheral T-cell lymphoma is underway. In addition, AFM13 is being investigated as combination partner, with a checkpoint inhibitor and adoptive NK cells.

AFM24 targets EGFR on solid tumors. Its mechanism of action through the activation of NK cells and macrophages is differentiated from other EGFR-targeting therapies. A phase 1 study with AFM24 monotherapy is ongoing and a combination study with adoptive NK cells is in preparation.

Additionally, we are developing several novel ICE molecules with undisclosed tumor targets through partnered programs.

Tuba: List out your preclinical innate cell engagers targeting hematologic and solid tumors?

Andreas: The ROCK platform enables us to develop ICE molecules for various tumor targets. The platform's modularity allows us to customize the ICEformats according to tumor targets, PK and other characteristics.

AFM28 and AFM32 are currently being developed to treat several undisclosed targets. We recently licensed AFM32 to Roivant Sciences for an upfront consideration of $60 million, with options to develop additional ICEmolecules for new tumor targets not included in our current pipeline.

We are excited about this partnership as it further validates our platform and scientific expertise in the selection of promising targets to develop ICE molecules in oncology indications where there is an unmet need.

Tuba: Can you highlight Affimed's alliances with other global companies? Is Affimed looking for more collaborations to develop its clinical programs?

Andreas: We are always looking for opportunities to explore innovative collaborations to further accelerate our robust pipeline and support our vision of stopping cancer from derailing patients lives.

In 2018 we entered a collaboration with Genentech that has proven to be very fruitful.

In 2020 we announced new collaborations with leaders in the field of NK cell products NKMax America and Artiva Biotherapeutics and with Roivant Sciences.

Our partnerships with NKMax America and Artiva will explore the potential of combining ICE molecules with NK cell products to maximize innate immune responses. We have granted Roivant license to AFM32 with options for additional ICE molecules directed against targets beyond our current pipeline.

Tuba: Do you think Affimed's therapies can overcome the limitations and challenges faced by current I-O therapies?

Andreas: Immuno-oncology is a broad field presenting multiple areas of scientific innovation, advancement and discovery. While current immuno-oncology therapies largely ignore the innate immune system, we believe it provides new opportunities for long-lasting, multi-layered tumor control. In addition to activating innate immune cells for directed tumor cell killing, the innate immune system stimulates the cross-talk to adaptive immune cells, triggering a total immune response.

The differentiated mechanism of action of our ICE molecules is designed for improved tolerability.

Tuba: AFM13 holds promise as monotherapy and in combinations. Comment over the statement.

Andreas: As demonstrated by our recent presentation at the American Society of Hematology virtual meeting, AFM13 was well-tolerated as a monotherapy and reached a high objective response rate among heavily pretreated patients with CD30-positive lymphoma. A registration-directed Phase 2 study with AFM13 as a monotherapy in patients with CD30-positive peripheral T-cell lymphoma is currently ongoing.

In addition, AFM13 is also being explored as a combination therapy. Recently published in Blood, a Phase 1b study with AFM13 and Merck's KEYTRUDA (pembrolizumab) achieved a complete response rate (CR) of 46 percent and an overall response rate (ORR) of 88 percent in patients with relapsed or refractory Hodgkin lymphoma. As a monotherapy, KEYTRUDA demonstrated an ORR of 69 percent and a CR of 22.4 percent. These data support the scientific rationale for combining innate cell engagers with checkpoint inhibitors.

A Phase 1 study with AFM13 in combination with adoptive NK cells was initiated in 2020. Pre-clinical data of this combination have been promising, revealing the potential benefits that preloading an NK cell product with an ICE® could have in the treatment of patients suffering from blood cancers.

Main Image Source: Edward Elmurst Health

About Author:

Dr. Andreas Harstrick is the CMO at Affimed. He has more than 30 years of extensive experience in cancer drug development, including strategic leadership of three global phases 3 programs of new biological entities that culminated in global regulatory approval, and multiple pivotal phases 3 studies.

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