RESEARCH & DEVELOPMENT

BioMed Valley Discoveries engages in research and development projects with intent to address unmet clinical needs across a variety of diseases and therapy modalities.

In our first decade, we have investigated research and development opportunities across a number of disease states, including a variety of compounds and mechanisms in the areas of oncology and immuno-oncology. These projects have included multiple mechanistic approaches:

  • Bacterial destruction of tumors from the inside out
  • Small molecules that target pathways critical to cancer cell growth, proliferation, and survival
  • Antibodies and antibody-drug conjugates that target and attack unique components of the cancer microenvironment

Our focus on critical unmet patient needs continues to drive our future research. Although our current programs focus on the development of therapies in the areas of oncology and immuno-oncology, we consider research and development opportunities across a number of disease states, modalities, and mechanisms.

We seek to work with innovative partners and collaborators to find creative solutions to drug development challenges. We also consider in-licensing opportunities and out-licensing partnerships.

CURRENT PROGRAMS

Our current therapeutic development programs represent a multi-faceted approach to eradication of tumors through direct targeting of cancer cells as well as components of the tumor microenvironment.

Clostridium novyi-NT (CNV-NT/BVD-550)— Tumor-fighting Bacteria

Source: In-licensed from Johns Hopkins University
Stage: Phase I

As tumors continue to grow, regions within the tumors become starved of nutrients and oxygen (hypoxic), and start to grow more slowly, lie dormant, or die (become necrotic). Hypoxic, slow-growing, and necrotic tumor cells are often resistant to radiation therapy and chemotherapy, however, this is an ideal environment for anaerobic bacteria that thrive in low oxygen conditions.

Based on this biology, BioMed Valley Discoveries is studying a new way to combat cancer—one that exploits the unusual conditions inside the tumor using CNV-NT (BVD-550), a tumor-fighting bacteria that is injected into tumors to kill the cancer from the inside out. Preclinical research has shown that CNV-NT (BVD-550) can destroy cancer cells in low-oxygen areas of tumors while leaving well-oxygenated tissue unharmed. The tumor-fighting bacteria can then be controlled using commonly available antibiotics.

While this approach to cancer treatment may sound unconventional, there is a long history of scientific study behind it. In the 1890s, physician William B. Coley observed that some cancer patients who underwent surgery and developed a bacterial infection afterward became completely cured of their tumors. Then, in the 1950s and 1960s, researchers tried using an anaerobic bacterium, Clostridium butyricum (C. butyricum), to fight cancer. Although C. butyricum destroyed large portions of tumors, scientists at the time could not adequately control the adverse effects of the bacteria or the toxins produced by the bacteria. As a result, the use of anaerobic bacteria to treat tumors was put on hold while radiation and chemotherapy emerged as standard treatments.

More recently, Bert Vogelstein’s laboratory at Johns Hopkins University returned to the study of bacteria as a possible cancer treatment using a strain of Clostridium novyi from which a lethal toxin was removed (C. novyi-NT/BVD-550). In one preclinical research study, tumor tissue was destroyed and did not return during the follow-up period in about 30% of animals treated. In addition to destroying tumor cells, the bacteria have been shown to provoke the animal’s immune system to attack cancer cells.

Building on these promising results, we advanced CNV-NT (BVD-550) to Phase I clinical trials to investigate the effects in patients with inoperable tumors. These trials established a recommended Phase II dose that is now being used in combination with pembrolizumab (NCT03435952). While many years of challenging work remain, our hope is that this work will someday lead to a new class of therapies to combat cancer, attacking tumors from the inside out.

Presentations and literature on CNV-NT (BVD-550):

28th EORTC-NCI-AACR Symposium Abstract | Poster

13th International Congress on Targeted Anticancer Therapies Abstract | Poster

Intratumoral Injection of Clostridium novyi-NT Spores induces antitumor responses. Roberts NJ et al. Sci Transl Med. 2014;6:249ra111. Abstract

Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors.  Janku F et al. Clin Cancer Res. 2021;27(1):96-106.
Abstract

CNV-NT (BVD-550) Trials

Ulixertinib (BVD-523): A Targeted Inhibitor of the MAPK Pathway

Source: In-licensed from large biotechnology company
Stage: Phase II

The mitogen-activated protein kinase (MAPK) pathway is a major intracellular signaling mechanism that controls growth, proliferation, and survival of cells. Numerous different cancers have been associated with mutations and subsequent abnormal activation of this pathway, making the cancers highly dependent on this pathway for their survival and growth.

The extracellular signal-regulated kinase (ERK) is the terminal master kinase in the MAPK pathway. BioMed Valley Discoveries is testing whether ulixertinib (BVD-523), a novel targeted cytotoxic designed to inhibit ERK, can be used to treat cancers that harbor mutations in the MAPK signaling pathway.

A large body of clinical experience has shown successful inhibition and disease control with a variety of inhibitors of other members of the MAPK pathway upstream of ERK (BRAF and MEK). Unfortunately, these same studies have also demonstrated that patients given targeted therapies often develop tumors that are resistant to a drug that was initially effective. Because of this, understanding resistance mechanisms and selecting targeted treatment regimens that can overcome or prevent resistance in the first place represent a major opportunity for effective treatment.

Our ERK inhibitor is a potent, selective small molecule that has demonstrated impressive in vitro and in vivo preclinical efficacy, and is expected to be effective in cancer settings where MAPK pathway dependence has been demonstrated. Beyond its use as a single-agent, front-line therapy, we plan to assess whether ulixertinib (BVD-523) may be effective as part of novel combination therapy regimens, as well as in patients with specific genetic profiles that accompany acquired resistance. Because of ERK’s downstream position in the pathway we believe that its inhibition may provide durable efficacy that is less often complicated by acquired drug resistance. In summary, targeting ERK with ulixertinib (BVD-523), either alone or in combination with other drugs, should be a valuable strategy to safely treat cancers that exhibit abnormal MAPK pathway activity.

Presentations and literature on ulixertinib (BVD-523):

2022 AACR Annual Meeting Poster 404 | Poster 415 | Poster 1057 | Poster 4022 | Press Release

2017 ASCO Annual Meeting Abstract | Presentation | Press Release

2017 AACR Annual Meeting Abstract | Presentation

2015 ASCO Annual Meeting Abstract | Presentation | Related video

2015 AACR Annual Meeting Abstract | Presentation

Ulixertinib (BVD-523)

CD276-ADC & TEM8-ADC: Dual-compartment Targeting for Cancer Ablation

Source: Cooperative research and development agreement with National Cancer Institute
Stage: Pre-IND

The cell-surface protein CD276/B7-H3 is broadly overexpressed by a wide variety of cancer cells as well as on the tumor-infiltrating blood vessels associated with those cells. Due to this dual-compartment expression, CD276-directed ablation of both the primary tumor cell as well as the supporting tumor blood supply could prove to be an extremely effective therapeutic approach.

An additional cell-surface protein, tumor endothelial marker 8 (TEM8), is overexpressed on cancer-associated fibroblasts and endothelium and provides a separate target for the tumor microenvironment. Based on this, BioMed Valley Discoveries is exploring the use of both CD276 antibody- and TEM8 antibody-drug conjugates (ADCs) as therapeutic agents to target multiple solid tumor types.

Antibody-drug conjugates (ADCs) represent a promising anti-cancer strategy in which the antibody directs targeted, selective localization of a toxic payload. Preclinical studies have shown that CD276- and TEM8-directed ADCs armed with different toxic payloads were able to destroy cancer cells with or without destruction of the associated blood supply depending on the nature of the toxin associated with it. Since the overexpression of these tumor antigens is associated with many different tumor types, this approach could impact a large variety of disease states.

References:

Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature. Seaman S et al. Cancer Cell. 2017;31:501-515.e8. Abstract | Commentary

Tumor stroma–targeted antibody-drug conjugate triggers localized anticancer drug release Szot C et al. JCI. 2018 Abstract

Translational medicine: doing things differently. Biopharma Deal. 2021. | PDF

CLINICAL TRIALS

BioMed Valley Discoveries’ clinical programs are associated with the following studies:

CNV-NT (BVD-550) Clinical Trials

Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores to Treat Patients With Solid Tumors That Have Not Responded to Standard Therapies
Condition: Solid Tumor Malignancies
Status: This study has been completed
More information

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT
Condition: Various Neoplasms
Status: Recruiting participants
More information

CNV-NT(BVD-550) Program

Ulixertinib (BVD-523) Clinical Trials

Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
Condition: Advanced Solid Tumors
Status: This study has been completed
More information

Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers
Condition: Healthy
Status: This study has been completed
More information

Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes
Conditions: Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Status: This study has been completed
More information

A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
Conditions: Uveal Melanoma
Status: This study is ongoing, but not recruiting participants
More information

Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors
Conditions: Solid Tumors, Pancreatic Cancer
Status: Recruiting participants
More information

Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas
Condition: Gastrointestinal Neoplasms
Status: Recruiting participants
More information

Study of Ulixertinib for Patients with Advanced Malignancies Harboring MEK or Atypical BRAF Alterations
Condition: Advanced Solid Tumors
Status: Recruiting participants
More information

Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies
Conditions: Compassionate use in advanced cancer patients with MAPK pathway-altered solid tumor(s)
Status: Available
More information

Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies
Conditions: Solid Tumors, Gastrointestinal Cancer
Status: Not yet recruiting
More information

Ulixertinib (BVD-523) Program

COMMITMENT TO PATIENTS

The needs of patients motivate us daily. Science and empirical evidence drive our research and development process toward improving patient care and quality of life. Our goal is to develop distinctive therapies that represent major advances in patient care.

In early-stage development, we provide an opportunity for patients to participate in clinical trials to help advance understanding of diseases and potential treatments. We seek input and guidance from patient organizations to help develop clinical trial protocols that meet patient needs, while providing valid scientific information.