Corporate Strategy



Identify cancers with a single, and clear, oncogenic driver


Evaluate sub-populations of cancer populations with an unmet need, where standards of care are ineffective


A global scientific and thought-leader network for new asset and technology identification for program acquisitions



Capital efficiency with a core executive team driving third-party research, manufacture and development partners


EGFR / HER Exon 20 Non-Small Cell Lung Cancer (NSCLC)

Approximately 6,500 patients in the US are diagnosed annually with EGFR and other HER-family Exon 20 insertion mutations in NSCLC(1). Unfortunately, these patients exhibit poor responses to standard EGFR tyrosine kinase inhibitors (TKIs).

EGFR Exon 20 insertion mutations present a distinct challenge from the group of classical, sensitizing EGFR mutations in lung cancer. Notably, the classical EGFR mutations, including deletions in exon 19 (del19) or the L858R mutations, have been successfully addressed by various commercial EGFR inhibitors, as these classical mutations are uniquely sensitive to inhibition versus wildtype EGFR(2). In contrast to the wildtype EGFR receptor, classical EGFR mutations exhibit increased binding affinity to tyrosine kinase inhibitors, but lower binding affinity to ATP. Therefore, conventional EGFR inhibitors are able to leverage a natural therapeutic window for classical EGFR mutant cancers, yielding relatively less severe systemic toxicities.

EGFR Exon 20 insertion mutations, however, present a challenge in that they lack this innate therapeutic window. The binding affinities of EGFR Exon 20 for conventional inhibitors, and for ATP, resemble that of wildtype EGFR. Patients with wildtype EGFR, or wildtype-like EGFR mutant tumors, such as Exon 20 insertion mutations, may present challenges in achieving meaningful drug concentrations to the site of the tumor while avoiding drug concentrations that are toxic in healthy tissues.

A novel solution to this problem would be a mechanism that achieves tumor-selectivity with a potent tyrosine kinase inhibitor capable of inhibiting wildtype and mutant EGFR.

  1. American Cancer Society NSCLC incidence of 183,000 patients per year; Hirano et al., Oncotarget. 2015; 6(36): 38789–38803; Peters and Zimmerman, Transl Lung Cancer Res. 2014 Apr; 3(2): 84–88
  2. Yasuda et al., Sci Transl Med. 2013; 5(216): 216ra177

Tarloxotinib (Tarlox)

Tarloxotinib (Tarlox) is a hypoxia-activated prodrug (HAP) of a potent EGFR / HER inhibitor, and produces the active drug only under pathologically low-oxygen (hypoxic) conditions. Tarlox, the inactive prodrug, gains an electron through a membrane-bound reductase, and in the absence of the electron being scavenged by oxygen, rapidly fragments into the active moiety, Tarlox-TKI. While Tarlox and Tarlox-TKI are cleared rapidly from plasma, with a half-life of ~1 hour, Tarlox-TKI has a half-life of over 80 hours in the tumor. In the presence of oxygen, oxygen removes the acquired electron, stabilizing the inactive Tarlox, avoiding the production of the active moiety in oxygenated tissues.

The ability to avoid producing the active drug in non-hypoxic regions leads to a sparing of healthy tissue, and avoidance of the common EGFR-related toxicities, typically in the digestive tract or skin. By sparing normoxic tissues, debilitating toxicities frequently observed with systemic EGFR inhibition, such as diarrhea, rash and pruritis may be avoided. Clinical studies of Tarlox demonstrate that the occurrence of diarrhea, rash and pruritis (itching) are twice to five times less likely than other EGFR inhibitors in development for Exon 20 tumors.

At the University of Colorado, animal models of EGFR Exon 20 tumors have demonstrated potent tumor regression at safe dose levels. Patient-derived xenograft models treated with Tarlox undergo rapid tumor regression, demonstrating appropriate prodrug conversion to Tarlox-TKI and sufficient TKI concentration in the tumor.


Physiologic Oxygen (Normoxic): Tarlox (prodrug) gains an electron (black circle) to produce a reactive intermediate, however oxygen quickly scavenges the electron to revert the intermediate to inactive Tarlox

Low Oxygen (Hypoxic): Absence of oxygen enables the loose electron to shift positions on Tarlox leading to fragmentation into the trigger moiety (dark blue structure) and a highly lipid-soluble Tarlox-TKI (light blue structure), with the TKI now able to enter the cell




Avanish Vellanki, MBA, MBS

Cofounder, Chairman and CEO

Robert Doebele, MD, PhD

Cofounder, Chair of the Scientific Advisory Board


Board of Directors

Avanish Vellanki, MBA, MBS (Chair)
Gorjan Hrustanovic, PhD
Tran Nguyen, MBA
Peter Radovich, MBA
Franklin M. Berger, CFA (Observer)


Scientific Advisory Board

Robert Doebele, MD, PhD (Chair)
Lori A. Kunkel, MD
Christopher Kirk, PhD
Adam Patterson, PhD
Jeff Smaill, PhD





Rain Therapeutics Inc. ("Rain") is committed to empowering leaders with an entrepreneurial spirit that thrive in small team environments. Our hiring strategy requires recruiting top talent that seek an opportunity to tackle tasks independently, and develop creative solutions across the business. Our employees need to be passionate about developing therapies in cancer to save lives.

Rain is an equal opportunity employer. All qualified applicants will be considered without regard to age, race, color, sex, religion/creed, national origin, marital status, ancestry, citizenship, military, reservist or veteran status, pregnancy, sexual orientation or preference, gender identity, gender expression, physical or mental disability, genetic predisposition or carrier status, or any other category protected under applicable federal, state or local law.

If you are interested in joining the Rain team, please contact us at careers@rainthera.com




Rain Therapeutics
47000 Warm Springs Blvd
Ste 1-370
Fremont, CA 94539

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