Recombination Therapeutics
Recombination Therapeutics
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Eliminating Cancer by Targeting the DNA Damage Response (DDR)

Eliminating Cancer by Targeting the DNA Damage Response (DDR) Eliminating Cancer by Targeting the DNA Damage Response (DDR) Eliminating Cancer by Targeting the DNA Damage Response (DDR)
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About Us

Recombination Therapeutics (RTx) is a precision oncology company focused on eliminating cancer by targeting DDR factors to overcome cancer drug resistance in genetically defined patient populations. 

DNA polymerase Theta (Polq)

  • Polq is a multi-functional DNA repair factor that is essential for the survival of homologous recombination (HR) deficient (HRD) cancer cells, such as those mutated in the BRCA1/2 tumor suppressor proteins. Polq is dispensable for normal cells, and is therefore an ideal drug target. Polq also promotes cellular resistance to various  cancer therapies, such as ionizing radiation, topoisomerase inhibitors and PARP inhibitors (PARPi). RTx is currently evaluating our Polq drug candidate in vivo.

Undisclosed target

  • Although PARP inhibitors (PARPi) have revolutionized precision oncology for HRD cancers, less than 60% of patients respond to PARPi, and patients frequently develop resistance to PARPi. Major mechanisms of PARPi resistance involve cellular reactivation of homologous recombination (HR). RTx is currently developing a potentially first-in-class small-molecule inhibitor of an enzyme that confers strong resistance to PARPi in both HR-deficient and HR-proficient cancer cells.

OUR TEAM

Richard Pomerantz, PhD Cofounder, CSO

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

Xiaojiang Chen, PhD Cofounder, Director of Structure Biology

  • Professor of Biochemistry and Molecular Biology, Thomas Jefferson University
  • Leader in DNA replication and repair; discovered mechanism of Polq-mediated DNA end-joining.

Xiaojiang Chen, PhD Cofounder, Director of Structure Biology

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

Xiaojiang Chen, PhD Cofounder, Director of Structure Biology

  •  Professor, Director NanoBiophysics and Structural Biology Center, University of Southern California
  • Leader in structural biology of DNA replication and repair; expert in structure-based drug design.

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

  • Professor, Temple University School of Pharmacy
  • Associate Director, Moulder Center for Drug Discovery Research
  • Expert in medicinal chemistry and drug development. Former leader at Pfizer and Wyeth Pharmaceuticals, Inc. 

John Oates Cofounder, CEO

Mercy Ramanjulu, Senior Chemist

Wayne Childers, PhD Cofounder, Director of Medicinal Chemistry

  •  Over 20 years in life sciences providing operational and financial leadership.  Deep domain experience in building and growing early stage organizations from early development through exit. 
  • COO Opsidio
  • GM United Biosource Biotechnology Solutions
  • COO & CFO, BioCor.
  • Active biotechnology angel investor.

Mercy Ramanjulu, Senior Chemist

Mercy Ramanjulu, Senior Chemist

Mercy Ramanjulu, Senior Chemist

  • Medicinal chemist with over 25 years of experience in industry (Pfizer, Bristol-Myers Squibb) and academia.

Highlighted research articles by RTx cofounders

Polθ reverse transcribes RNA and promotes RNA-templated DNA repair. Chandramouly G, Zhao J, McDevitt S, Rusanov T, Hoang T, Borisonnik N, Treddinick T, Lopezcolorado FW, Kent T, Siddique LA, Mallon J, Huhn J, Shoda Z, Kashkina E, Brambati A, Stark JM, Chen XS, Pomerantz RT. Sci Adv. 2021 Jun 11;7(24):eabf1771. doi: 10.1126/sciadv.abf1771. Print 2021 Jun.PMID: 34117057

https://advances.sciencemag.org/content/7/24/eabf1771



Polθ promotes the repair of 5'-DNA-protein crosslinks by microhomology-mediated end-joining. Chandramouly G, Liao S, Rusanov T, Borisonnik N, Calbert ML, Kent T, Sullivan-Reed K, Vekariya U, Kashkina E, Skorski T, Yan H, Pomerantz RT.Cell Rep. 2021 Mar 9;34(10):108820. doi: 10.1016/j.celrep.2021.108820.PMID: 33691100 

https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00134-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124721001340%3Fshowall%3Dtrue



Molecular basis of microhomology-mediated end-joining by purified full-length Polθ. Black SJ, Ozdemir AY, Kashkina E, Kent T, Rusanov T, Ristic D, Shin Y, Suma A, Hoang T, Chandramouly G, Siddique LA, Borisonnik N, Sullivan-Reed K, Mallon JS, Skorski T, Carnevale V, Murakami KS, Wyman C, Pomerantz RT.Nat Commun. 2019 Sep 27;10(1):4423. doi: 10.1038/s41467-019-12272-9.PMID: 31562312

https://www.nature.com/articles/s41467-019-12272-9



Polymerase θ-helicase efficiently unwinds DNA and RNA-DNA hybrids. Ozdemir AY, Rusanov T, Kent T, Siddique LA, Pomerantz RT.J Biol Chem. 2018 Apr 6;293(14):5259-5269. doi: 10.1074/jbc.RA117.000565. Epub 2018 Feb 14.PMID: 29444826

https://www.jbc.org/article/S0021-9258(20)40998-6/fulltext



Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ. Kent T, Chandramouly G, McDevitt SM, Ozdemir AY, Pomerantz RT.Nat Struct Mol Biol. 2015 Mar;22(3):230-7. doi: 10.1038/nsmb.2961. Epub 2015 Feb 2.PMID: 25643323

https://www.nature.com/articles/nsmb.2961



The structure of APOBEC1 and insights into its RNA and DNA substrate selectivity. Wolfe AD, Li S, Goedderz C, Chen XS.NAR Cancer. 2020 Dec;2(4):zcaa027. doi: 10.1093/narcan/zcaa027. Epub 2020 Oct 9.PMID: 33094286

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556403/



Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G. Yang H, Ito F, Wolfe AD, Li S, Mohammadzadeh N, Love RP, Yan M, Zirkle B, Gaba A, Chelico L, Chen XS.Nat Commun. 2020 Jan 31;11(1):632. doi: 10.1038/s41467-020-14377-y.PMID: 32005813

https://www.nature.com/articles/s41467-020-14377-y



Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H.

Ito F, Yang H, Xiao X, Li SX, Wolfe A, Zirkle B, Arutiunian V, Chen XS.Sci Rep. 2018 Feb 28;8(1):3763. doi: 10.1038/s41598-018-21955-0.PMID: 29491387

https://www.nature.com/articles/s41598-018-21955-0



Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Gai D, Zhao R, Li D, Finkielstein CV, Chen XS.Cell. 2004 Oct 1;119(1):47-60. doi: 10.1016/j.cell.2004.09.017.PMID: 15454080

https://www.cell.com/cell/fulltext/S0092-8674(04)00890-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867404008906%3Fshowall%3Dtrue



Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.

Zhang H, Pandey S, Travers M, Sun H, Morton G, Madzo J, Chung W, Khowsathit J, Perez-Leal O, Barrero CA, Merali C, Okamoto Y, Sato T, Pan J, Garriga J, Bhanu NV, Simithy J, Patel B, Huang J, Raynal NJ, Garcia BA, Jacobson MA, Kadoch C, Merali S, Zhang Y, Childers W, Abou-Gharbia M, Karanicolas J, Baylin SB, Zahnow CA, Jelinek J, Graña X, Issa JJ.Cell. 2018 Nov 15;175(5):1244-1258.e26. doi: 10.1016/j.cell.2018.09.051. Epub 2018 Oct 25.PMID: 30454645

https://www.cell.com/cell/fulltext/S0092-8674(18)31263-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418312637%3Fshowall%3Dtrue



Discovery and SAR of Novel Disubstituted Quinazolines as Dual PI3Kalpha/mTOR Inhibitors Targeting Breast Cancer. Al-Ashmawy AAK, Elokely KM, Perez-Leal O, Rico M, Gordon J, Mateo G, Omar AM, Abou-Gharbia M, Childers WE Jr.ACS Med Chem Lett. 2020 Oct 12;11(11):2156-2164. doi: 10.1021/acsmedchemlett.0c00289. eCollection 2020 Nov 12.PMID: 33214824

https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00289



Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia. Hewlett E, Toma M, Sullivan-Reed K, Gordo J, Sliwinski T, Tulin A, Childers WE, Skorski T.Med Chem Res. 2020 Jun;29(6):962-978. doi: 10.1007/s00044-020-02537-0. Epub 2020 Apr 19.PMID: 33071527

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560981/



Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin. Lounsbury N, Eidem T, Colquhoun J, Mateo G, Abou-Gharbia M, Dunman PM, Childers WE.Bioorg Med Chem Lett. 2018 Apr 1;28(6):1127-1131. doi: 10.1016/j.bmcl.2018.01.022. Epub 2018 Jan 31.PMID: 29463447

https://www.sciencedirect.com/science/article/abs/pii/S0960894X18300325?via%3Dihub



A Mitochondrial-targeted purine-based HSP90 antagonist for leukemia therapy. Bryant KG, Chae YC, Martinez RL, Gordon JC, Elokely KM, Kossenkov AV, Grant S, Childers WE, Abou-Gharbia M, Altieri DC.Oncotarget. 2017 Dec 11;8(68):112184-112198. doi: 10.18632/oncotarget.23097. eCollection 2017 Dec 22.PMID: 29348817

https://www.oncotarget.com/article/23097/text/



Prodrugs of perzinfotel with improved oral bioavailability. Baudy RB, Butera JA, Abou-Gharbia MA, Chen H, Harrison B, Jain U, Magolda R, Sze JY, Brandt MR, Cummons TA, Kowal D, Pangalos MN, Zupan B, Hoffmann M, May M, Mugford C, Kennedy J, Childers WE Jr.J Med Chem. 2009 Feb 12;52(3):771-8. doi: 10.1021/jm8011799.PMID: 19146418

https://pubs.acs.org/doi/10.1021/jm8011799







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