All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the International Myeloma Foundation or HealthTree for Multiple Myeloma.

The Multiple Myeloma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Introducing

Now you can personalise
your Multiple Myeloma Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

The Multiple Myeloma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Multiple Myeloma Hub cannot guarantee the accuracy of translated content. The Multiple Myeloma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
LOADING
You're logged in! Click here any time to manage your account or log out.
LOADING
You're logged in! Click here any time to manage your account or log out.

The Multiple Myeloma Hub is an independent medical education platform, sponsored by Bristol Myers Squibb, GSK, Johnson & Johnson, Pfizer, Roche and Sanofi. The levels of sponsorship listed are reflective of the amount of funding given. Digital educational resources delivered on the Multiple Myeloma Hub are supported by an educational grant from Janssen Biotech, Inc. View funders.

2022-05-18T08:42:50.000Z

BHV-1100, a bispecific antibody recruiting molecule

May 18, 2022
Share:
Learning objective: After reading this article, learners will be able to cite a new clinical development in multiple myeloma.

Bookmark this article

Within the field of targeted immunotherapies, novel strategies to direct immune effectors against multiple myeloma (MM) cells continue to be explored. Current challenges include identifying new targets, simplifying and improving manufacturing processes and access, and facilitating the administration of immunotherapeutic agents without compromising their efficacy and while prioritizing a safe profile.1

BHV-1100 (previously known as KP1237) is an antibody-recruiting molecule (ARM).2,3 ARMs bind to endogenous antibodies and direct them toward cancerous cells.2 Fully synthetic ARMs offer advantages over traditional biologics, such as monoclonal antibodies, including the potential for oral administration.2 In the case of BHV-1100, the ARM platform provides a bispecific antigen-targeting to endogenous antibodies and MM cells.2

Mechanism of action

As part of the innate immune system, natural killer (NK) cells target and show a strong cytolytic function against physiologically stressed cells, such as cancer cells; however, tumor cells can evade detection.2 BHV-1100 targets the MM cell-surface protein CD38 and recruits NK cells to destroy the tumor.2 As a bispecific molecule, BHV-1100 binds to both CD38 and human immunoglobulin (Ig), as shown in Figure 1.2 When close, NK cells bind to the Fc portion of Ig and activate the antibody-dependent tumor lysis.2 To enhance this effect, BHV-1100 can be combined with primed autologous cytokine-induced memory-like (CIML) NK cells. Rastelli et al. have shown a statistically significant increase in specific killing when BHV-1100 and CIML NK are combined ex vivo, without the necessity for genetic engineering.3

Figure 1. The mechanism of action of BHV-1100*

A The structure of BHV-1100. B BHV-1100 binds to Ig and CD38 receptors on MM cells, recruiting NK cells and activating antibody-dependent tumor lysis.
Ig, immunoglobulin; MM, multiple myeloma; NK, natural killer.
*Adapted from Biohavenpharma.com.2

Regulatory status

An ongoing phase Ia/Ib clinical trial (NCT04634435) is assessing potential adverse events associated with BHV-1100 and its initial efficacy in newly diagnosed patients with MM eligible for autologous hematopoietic stem cell transplant (auto-HSCT).4 The trial is enrolling patients in first remission before auto-SCT who have minimal residual disease; patients receive BHV-1100 in combination with CIML NK cells and low-dose interleukin-2 (IL-2).4 The estimated primary completion date is June 30, 2023.4 The U.S. Food and Drug Administration (FDA) has previously provided orphan drug designation for BHV-1100 in MM.5

  1. Rodriguez-Lobato LG, Oliver-Caldes A, Moreno DF, et al. Why immunotherapy fails in multiple myeloma. Hemato. 2021; 2(1):1-42. DOI: 10.3390/hemato2010001
  2. Biohaven Pharmaceuticals. Biohaven enrolls phase 1a/1b clinical trial of BHV-1100, lead asset from its ARMTM (antibody recruiting molecule) platform, in combination with NK cell therapy for the treatment of multiple myeloma. https://www.biohavenpharma.com/investors/news-events/press-releases/10-27-2021. Published Oct 27, 2021. Accessed May 5, 2022.
  3. Rastelli L, Mohsin M, Rossi AM, et al. A first-in-class ex vivo combination between cytokine-induced memory like (CIML) NK cells and a CD38 targeting antibody recruiting molecule (ARM) as a novel approach to target NK cells without cellular engineering for the treatment of multiple myeloma. J Clin Oncol. 2020;38(15_suppl):8523-8523. DOI: 1200/JCO.2020.38.15_suppl.8523
  4. ClinicalTrials.gov. Autologous memory-like NK cell therapy with BHV-1100 (formerly KP1237), low dose IL-2 in multiple myeloma patients. https://clinicaltrials.gov/ct2/show/study/NCT04634435. Updated Jan 19, 2022. Accessed May 16, 2022.
  5. GlobeNewswire. Kleo Pharmaceuticals announces orphan drug designation for KP1237 in multiple myeloma. https://www.globenewswire.com/news-release/2020/09/08/2090094/0/en/Kleo-Pharmaceuticals-Announces-Orphan-Drug-Designation-for-KP1237-in-Multiple-Myeloma.html. Published Sep 8, 2020. Accessed May 5, 2022.

Your opinion matters

On average, how many patients with multiple myeloma do you see in a month?
4 votes - 37 days left ...

Newsletter

Subscribe to get the best content related to multiple myeloma delivered to your inbox