Developing Innovative Therapies for the Treatment of Cancer

XRad Therapeutics is a privately-held, clinical stage biopharmaceutical company focused on developing dual kinase inhibitors for treating cancer. The company’s lead product, XRD-0394, is currently being evaluated in the clinic.

XRD-0394

XRD-0394, is a first-in-class dual inhibitor of ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK). Initial development efforts are focused on evaluating XRD-0394’s ability to enhance radiation therapy when used in combination. In parallel, the company is exploring the potential benefits of using XRad’s dual kinase inhibitors in combination with targeted radionuclides, immune checkpoint inhibitors, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors and antibody drug conjugates (ADCs).

Science

All cells in the human body are susceptible to DNA damage which may result from a variety of sources including radiation, chemotherapy, UV light and reactive oxygen species. To maintain genomic integrity, cells have developed several, sophisiticated mechanisms to repair this damage which is collectively referred to as the DNA Damage Response (DDR).

While it is critical for healthy cells to effectively repair DNA damage, there are instances when inducing severe DNA damage or preventing DNA repair in unhealthy cells, such as tumor cells, is beneficial. For example, radiation therapy is the most widely used cancer therapy and works by causing severe DNA damage to tumor cells in the form of double-stranded breaks which ultimately leads to cell death.

In addition to radiation therapy, recent research has shown that blocking certain enzymes in the DDR pathways shows promise as an emerging therapeutic strategy for treating cancer. Two targets of particular interest include ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK). Both ATM and DNA-PK are well-characterized, genetically-validated targets which play central roles in regulating cellular responses to DNA double-strand breaks.

Preclinical data have shown that inhibition of either ATM or DNA-PK (when combined with radiation therapy) results in a higher level of tumor cell death versus radiation therapy alone. Further, dual inhibition of both ATM and DNA-PK (when combined with radiation therapy) yields an even greater effect suggesting that dual inhibition of these targets could offer a potential therapeutic benefit.

Scientific Rationale for Dual Inhibition

ATM & DNA-PK play central roles in regulating the cell’s response to DNA damage. These enzymes appear to have compensatory relationships. Dual inhibition of both targets overcomes this effect.

Pipeline

Clinical Opportunities for XRad Dual-kinase Inhibitors

In addition to improved radiosensitization, inhibition of ATM and DNA-PK has additional therapeutic potential across several mechanistic pathways. XRad has generated encouraging preclinical data in these areas to better understand future applications.

Radiosensitization and Radiation Sparing

  • Opportunity to treat patients using lower doses of RT + XRD-0394
  • IMRT, SBRT, proton beam therapy, brachytherapy

RT + Immunotherapy

  • Phosphorylation of TBK1 is a marker of activation of the type 1 IFN response and has been linked to enhanced tumor response to immune checkpoint blockade therapy

Combination w/ ADCs

  • Combination with drug conjugates
  • Combination with radiopharmaceuticals

Combination w/ Other DDR Targets

  • Combination with other DDR targets including PARP

DDR Mutant Tumors

  • Opportunity for synthetic lethality (e.g., BRCA1 & BRCA2)

Clinical Trials

XRad is currently conducting a Phase 1 study to evaluate the safety and tolerability of single ascending doses of XRD-0394 administered with palliative RT in patients with metastatic, locally advanced or recurrent cancer.

The study is being conducted at two centers, Memorial Sloan Kettering Cancer Center and the Stanford Cancer Institute.

Our Team

XRad’s leadership brings together a powerful team with academic research, clinical practice and industry expertise, focused on the design, discovery and development of novel therapies targeting DNA damage repair.

Tona Gilmer, PhD

Position: President, CEO & Co-Founder

  • Former Global Director of Oncology Translational Research, GSK
  • Expertise in molecular/cellular biology, pharmacology, biomarker discovery
  • Experience in target ID through post-NDA approval
  • Key leader and member of research and project teams for Tykerb, Votrient, Tafinlar and Mekinist

Tona Gilmer, PhD

President, CEO & Co-Founder

Former Global Director of Oncology Translational Research, GSK Expertise in...

Michael Kastan MD, PhD

Position: Director & Co-Founder

  • Executive Director, Duke Cancer Institute (DCI)
  • Elected to National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences;
  • Leading expert in DNA damage & repair, tumor suppressor genes, and cancer causation related to genetic predisposition

Michael Kastan MD, PhD

Director & Co-Founder

Executive Director, Duke Cancer Institute (DCI) Elected to National Academy...

David Kirsch MD, PhD

Position: Clinical Advisor & Co-Founder

  • Prof Radiation Oncology & Pharmacology & Cancer Biology, Duke;
  • Vice Chair for Basic & Translational Research in Radiation Oncology & Leader of the Radiation Oncology & Imaging Program in DCI;
  • MD/PhD at J Hopkins; post-doc at MIT, Radiation Oncology at MGH

David Kirsch MD, PhD

Clinical Advisor & Co-Founder

Prof Radiation Oncology & Pharmacology & Cancer Biology, Duke; Vice...

Anthony Sun, MD

Position: Co-Founder

  • President and Chief Executive Officer for Zentalis Pharmaceuticals.
  • Fmr Partner at Aisling Capital and Perseus-Soros Biopharmaceutical Fund
  • BS in Electrical Engineering from Cornell University, an MD from Temple University School of Medicine, an MBA from the Wharton School of Business

Anthony Sun, MD

Co-Founder

President and Chief Executive Officer for Zentalis Pharmaceuticals. Fmr Partner...

Contact Us

If you are interested in partnering with XRad or have other business development inquiries, please get in touch.