Hummingbird Bioscience is developing antibodies against a number of important targets where we believe there is an opportunity create significant impact. All programs are either first in class or have a highly differentiated mechanism that offers the potential for best in class efficacy.
HMBD-001 Anti-HER3 Monoclonal Antibody
HMBD-001 represents a unique, highly-specific, anti-HER3 neutralising
antibody with a novel mechanism of action that offers significant potential
for broad clinical benefit. Previous attempts to block the HER3 receptor, a
key player in the signaling pathway that promotes cell division and tumor growth
in cancer, have not proven to be efficacious. HER3 is activated by the
binding of neuregulin (NRG1), which stabilizes a transient open conformation to allow it to
form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.
Preclinical models have shown that HMBD-001 is able to effectively bind to a difficult to target region on HER3 uniquely, blocking the heterodimerisation of HER3 with HER2/EGFR independent of NRG1 binding. This potently inhibits the activation of the signalling pathway – and consequently, tumour growth.Cancer Research UK has partnered with Hummingbird Bioscience to advance this novel antibody drug into clinical trials for the treatment of HER3-driven cancer. The clinical trial of this investigational candidate is expected to commence following regulatory submission approvals in the second half of 2020.
HMBD-002 Anti-VISTA Monoclonal Antibody
HMBD-002 represents a unique first-in-class anti-VISTA neutralising antibody. VISTA is a co-inhibitory immune checkpoint receptor of the B7 family that suppresses T-cell activity and has been shown to play a critical role in the formation of tumors and resistance to immunotherapy in cancer.
HMBD-002 binds to VISTA at a specific site predicted to be essential for ligand-binding and function, inhibiting VISTA and neutralising its activity in cancer cells.
Preclinical models have shown that a single dose of HMBD-002 as a monotherapy significantly reduces tumor progression, prolongs progression-free survival and inhibits tumor growth with no observed toxicity. Its application as combination therapy with antibodies against PD(L)-1 shows potential to more than double its efficacy.
The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded Hummingbird Bioscience a US$13.1 million product development grant to advance this first-in-class anti-VISTA therapeutic antibody into clinical trials for the treatment of solid tumours that are unresponsive to existing therapies and have their anti-tumour immunity suppressed by VISTA-mediated activity. The clinical trial of this investigational candidate is expected to commence following regulatory submission approvals in the second half of 2020.
Thakkar, D. Sancenon, V., Taguiam, M., Guan, S. Wu, Z., Ng, E., Paszkiewicz, K.H., Ingram, P.J., Boyd-Kirkup, J.D., 10D1F, an Anti-HER3 antibody that uniquely blocks the receptor heterodimerization interface, potently inhibits tumor growth across a broad panel of tumor models. Mol Cancer Ther. Epub 7 Jan 2020 10.1158/1535-7163.MCT-19-0515
Thakkar, D., Taguiam, M., Sancenon, V., Guan, S., Paszkiewicz, K., Ingram, P., Boyd-Kirkup, J. HMBD-001-10D1, A novel humanized anti-HER3 antibody with a unique mechanism of action, demonstrates superior tumor inhibition in multiple tumor models compared to other EGFR family therapies 87 EJC Vol 103 S1, Nov 2018.
Boyd-Kirkup, J.D., Thakkar, D., Sancenon, V., Guan, S., Paszkiewicz, K., & Ingram, P.J. Abstract: 477: HMBD-002-V4 A novel anti-VISTA antibody that uniquely binds murine and human VISTA and potently inhibits tumor growth by remodeling the immunosuppressive tumor microenvironment. J. Immunother. Cancer, vol 6, no. S1, p. 115, Nov. 2018. https://doi.org/10.1186/s40425-018-0423-x
Boyd-Kirkup, J. D., Thakkar, D., Paszkiewicz, K., & Ingram, P. J. (2018). Abstract 1729: Integrative immune profiling of syngeneic tumor models provides predictive immune signatures for treatment response with HMBD-002, a novel anti-VISTA neutralizing antibody. Cancer Research, 78(13 Supplement), 1729–1729. https://doi.org/10.1158/1538-7445.am2018-1729
Ingram, P. J., Thakkar, D., & Boyd-Kirkup, J. D. (2017). Abstract 587: HMBD-002, a novel neutralizing antibody targeting a specific epitope on the co-inhibitory immune checkpoint receptor VISTA, displays potent anti-tumor effects in pre-clinical models. Cancer Research, 77(13 Supplement), 587–587. https://doi.org/10.1158/1538-7445.AM2017-587
Boyd-Kirkup, J. D., Thakkar, D., & Ingram, P. J. (2017). Abstract 24: HMBD-001, a novel anti-ErbB3 antibody with a unique mechanism of action, effectively inhibits tumor growth in pre-clinical models of ErbB3+ solid tumors. Cancer Research, 77(13 Supplement), 24–24. https://doi.org/10.1158/1538-7445.AM2017-24
Boyd-Kirkup, J., Thakkar, D., Brauer, P., Zhou, J., Chng, W.-J., & Ingram, P. J. (2017). HMBD004, a Novel Anti-CD47xCD33 Bispecific Antibody Displays Potent Anti-Tumor Effects in Pre-Clinical Models of AML. Blood, 130(Suppl 1). https://ashpublications.org/blood/issue/130/Supplement%201