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  • Review Article
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Commercialization of regenerative-medicine therapies

Abstract

The clinical translation of regenerative-medicine products, including cell therapies, therapeutic tissue engineering products, and human cell and tissue products, remains limited because of the so-called ‘valley of death’, that is, the lack of resources necessary to move a product from early preclinical to clinical development. To advance more regenerative-medicine products into the clinic, academic researchers may benefit greatly from insights into the commercialization process, in particular, through academic startups. In this Review, we discuss key commercialization aspects, that is, protecting intellectual property, navigating regulatory pathways and obtaining funding, and highlight case studies of academic startups that have successfully developed US Food and Drug Administration-approved regenerative-medicine products and companies that have received Regenerative Medicine Advanced Therapy designations for their regenerative-medicine products in development.

Key points

  • Academic researchers interested in translating regenerative-medicine therapies to approved products may benefit from knowing about commercialization aspects early in research and development.

  • Understanding the steps toward establishing intellectual property (IP) within academic institutions is key to conducting and disseminating IP-yielding research.

  • Regenerative Medicine Advanced Therapy (RMAT) designations provide a pathway that can expedite the approval process of regenerative-medicine products.

  • Grants and non-dilutive mechanisms can support preclinical studies, and dilutive mechanisms of funding and initial public offerings are the major sources of financial capital for clinical development phases.

  • Academic institutions and funding agencies should implement policy changes to motivate and drive academic researchers toward the commercialization of regenerative-medicine technologies.

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Fig. 1: Steps toward obtaining patents and disseminating research findings while maintaining patenting rights.
Fig. 2: The FDA regulatory pathway for regenerative-medicine therapies.
Fig. 3: Funding mechanisms for academic startups.

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References

  1. Oberweis, C. V., Marchal, J. A., López-Ruiz, E. & Gálvez-Martín, P. A worldwide overview of regulatory frameworks for tissue-based products. Tissue Eng. B 26, 181–196 (2020).

    Article  Google Scholar 

  2. Jacques, E. & Suuronen, E. J. The progression of regenerative medicine and its impact on therapy translation. Clin. Transl. Sci. 13, 440–450 (2020).

    Article  Google Scholar 

  3. Goula, A. et al. Advanced therapy medicinal products challenges and perspectives in regenerative medicine. J. Clin. Med. Res. 12, 780–786 (2020).

    Article  Google Scholar 

  4. Sipp, D. & Okano, H. Japan strengthens regenerative medicine oversight. Cell Stem Cell 22, 153–156 (2018).

    Article  Google Scholar 

  5. Kim, D.-S. & Bae, S. Impact and challenges of enactment for advanced regenerative medicine in South Korea. Front. Bioeng. Biotechnol. 10, 972865 (2022).

    Article  Google Scholar 

  6. Qiu, T., Hanna, E., Dabbous, M., Borislav, B. & Toumi, M. Regenerative medicine regulatory policies: a systematic review and international comparison. Health Policy 124, 701–713 (2020).

    Article  Google Scholar 

  7. Hogle, L. F. & Das, A. The social production of evidence: regenerative medicine and the 21st Century Cures Act. Regen. Med. 12, 581–586 (2017).

    Article  Google Scholar 

  8. Brown, D. G. & Wobst, H. J. A decade of FDA-approved drugs (2010–2019): trends and future directions. J. Med. Chem. 64, 2312–2338 (2021).

    Article  Google Scholar 

  9. Butler, D. Translational research: crossing the valley of death. Nature 453, 840–842 (2008).

    Article  Google Scholar 

  10. Frederickson, R. M. Escaping the valley of death. Mol. Ther. 20, 476–478 (2012).

    Article  Google Scholar 

  11. Hinsenkamp, A., Benyó, Z. & Hornyák, I. Overview of tissue engineering patent strategies and patents from 2010 to 2020, including outcomes. Tissue Eng. B 28, 626–632 (2022).

    Article  Google Scholar 

  12. Allen-Hoffmann, L., Comer, A., Conrad, P. B., Hoffmann, M. & Ivarie, C. A.-R. Improved skin substitutes and uses thereof. Australian patent application 214639 B2 (2010).

  13. Asano, S., Nakanishi, Y. & Sugiyama, D. Intellectual property in the field of regenerative medicine in Japan. Clin. Ther. 40, 1823–1827 (2018).

    Article  Google Scholar 

  14. Pirnstill, J. & Allen-Hoffmann, B. L. Cold storage of organotypically cultured skin equivalents for clinical applications. US patent 10743533 B2 (2022).

  15. Allen-Hoffmann, B. L., Pirnstill, J. C., Gratz, K. R. & Comer, A. R. Cryopreservation of viable human skin substitutes. Australian patent 232795 B2 (2019).

  16. Koepsel, J. & Gratz, K. Tissue container systems. US patent application 0330542 A1 (2022).

  17. Smiell, J., Comer, A., Lokuta, M. & Allen-Hoffmann, B. L. Methods for treating acute wounds and improving outcomes. Australian patent application 353695 A1 (2020).

  18. Wang, S.-J. Patent portfolios for biotech inventions. Nat. Biotechnol. 31, 501–503 (2013).

    Article  Google Scholar 

  19. Rachinsky, T. First-to-invent versus first-to-file: impact of the AIA. Pharm. Pat. Anal. 3, 353–359 (2014).

    Article  Google Scholar 

  20. Begley, C. G. & Ioannidis, J. P. A. Reproducibility in science. Circ. Res. 116, 116–126 (2015).

    Article  Google Scholar 

  21. Ozyhar, T., Barnabei, L. & Myrick, D. When speed matters: a discussion on the benefits of a grace period in patent law to accelerate pharmaceutical innovation in times of pandemic. J. Law Biosci. 9, lsac004 (2022).

    Article  Google Scholar 

  22. Sherkow, J. S. Preprint servers and patent prior art. EMBO Rep. 23, e54439 (2022).

    Article  Google Scholar 

  23. Armstrong, J. P. K. et al. A blueprint for translational regenerative medicine. Sci. Transl. Med. 12, eaaz2253 (2020).

    Article  Google Scholar 

  24. Crama, P., Reyck, B. D. & Degraeve, Z. Milestone payments or royalties? Contract design for R&D licensing. Oper. Res. 56, 1539–1552 (2008).

    Article  MathSciNet  MATH  Google Scholar 

  25. Nordberg, R. C., Otarola, G. A., Wang, D., Hu, J. C. & Athanasiou, K. A. Navigating regulatory pathways for translation of biologic cartilage repair products. Sci. Transl. Med. 14, eabp8163 (2022).

    Article  Google Scholar 

  26. Zscharnack, M. et al. Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP). J. Transl. Med. 13, 160 (2015).

    Article  Google Scholar 

  27. Cox, E. M., Edmund, A. V., Kratz, E., Lockwood, S. H. & Shankar, A. Regulatory affairs 101: introduction to expedited regulatory pathways. Clin. Transl. Sci. 13, 451–461 (2020).

    Article  Google Scholar 

  28. Kulkarni, T. N. & Kulkarni, N. G. Authoring a periodic adverse drug experience report…here’s what you need to know! Perspect. Clin. Res. 10, 95–99 (2019).

    Article  Google Scholar 

  29. Alapati, D., Egan, P. & Holcombe, J. Understanding conflict of interest for academic entrepreneurs. In Academic Entrepreneurship for Medical and Health Scientists. PubPub Edition (2021).

  30. Collins, L. R. & Shepard, K. A. CIRM tools and technologies: breaking bottlenecks to the development of stem cell therapies. Stem Cell Transl. Med. 9, 1129–1136 (2020).

    Article  Google Scholar 

  31. Yuh, D. D. Value analysis committees: not just another committee to get out of. J. Thorac. Cardiovasc. Surg. 155, 686–687 (2018).

    Article  Google Scholar 

  32. Dang, A. & Kaur, K. Comparative effectiveness research and its utility in in-clinic practice. Perspect. Clin. Res. 7, 9–14 (2016).

    Article  Google Scholar 

  33. Westrich, K. D., Wilhelm, J. A. & Schur, C. L. Comparative effectiveness research in the USA: when will there be an impact on healthcare decision-making? J. Comp. Eff. Res. 5, 207–216 (2016).

    Article  Google Scholar 

  34. Carter, R. G. et al. Innovation, entrepreneurship, promotion, and tenure. Science 373, 1312–1314 (2021).

    Article  Google Scholar 

  35. Caulfield, T., Harmon, S. H. & Joly, Y. Open science versus commercialization: a modern research conflict? Genome Med. 4, 17 (2012).

    Article  Google Scholar 

  36. Tompkins, B. A. et al. IMPACT: Preclinical studies of cell therapy for human disease. Circ. Res. 122, 1006–1020 (2018).

    Article  Google Scholar 

  37. Ginty, P., Singh, P., Smith, D., Hourd, P. & Williams, D. Achieving reimbursement for regenerative medicine products in the USA. Regen. Med. 5, 463–469 (2010).

    Article  Google Scholar 

  38. Bubela, T. et al. Bringing regenerative medicines to the clinic: the future for regulation and reimbursement. Regen. Med. 10, 897–911 (2015).

    Article  Google Scholar 

  39. Marks, L. V. Collaboration — a competitor’s tool: the story of Centocor, an entrepreneurial biotechnology company. Bus. History 51, 529–546 (2009).

    Article  Google Scholar 

  40. Cheever, M. A. & Higano, C. S. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin. Cancer Res. 17, 3520–3526 (2011).

    Article  Google Scholar 

  41. Schmidt, C. Gintuit cell therapy approval signals shift at US regulator. Nat. Biotechnol. 30, 479–479 (2012).

    Article  Google Scholar 

  42. Schmidt, C. FDA approves first cell therapy for wrinkle-free visage. Nat. Biotechnol. 29, 674–675 (2011).

    Article  Google Scholar 

  43. Boss, W. K. et al. Autologous cultured fibroblasts as cellular therapy in plastic surgery. Clin. Plastic Surg. 27, 613–626 (2000).

    Article  Google Scholar 

  44. Morrison, C. Boom: 2018’s biotech IPOs. Nat. Rev. Drug Discov. 18, 3–6 (2019).

    Article  Google Scholar 

  45. Markert, M. L. et al. Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus. J. Immunol. 158, 998–1005 (1997).

    Article  Google Scholar 

  46. Markert, M. L. et al. Transplantation of thymus tissue in complete DiGeorge syndrome. N. Engl. J. Med. 341, 1180–1189 (1999).

    Article  Google Scholar 

  47. Markert, M. L. et al. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood 102, 1121–1130 (2003).

    Article  Google Scholar 

  48. Markert, M. Parathyroid and thymus transplantation in DiGeorge syndrome subjects. US patent 0041854 A1 (2009).

  49. Markert, M. L. Parathyroid and thymus transplantation in DiGeorge syndrome subjects. World patent application WO 107601 A3 (2006).

  50. Markert, M. L. Cultured thymus tissue transplantation promotes donor-specific tolerance to allogeneic solid organ transplants. World patent application WO 165197 A1 (2019).

  51. Markert, M. L. et al. Methods of determining the suitability of cultured thymus tissue for implantation into humans and associated methods of use. Canadian patent application 3150732 A1 (2021).

  52. Allen-Hoffmann, B. L. et al. Normal growth and differentiation in a spontaneously immortalized near-diploid human keratinocyte cell line, NIKS. J. Investig. Dermatol. 114, 444–455 (2000).

    Article  Google Scholar 

  53. Schurr, M. J. et al. Phase I/II clinical evaluation of stratagraft: a consistent, pathogen-free human skin substitute. J. Trauma. Acute Care Surg. 66, 866 (2009).

    Article  Google Scholar 

  54. US National Library of Medicine. StrataGraft™ skin tissue (human donor skin) in the surgical management of complex skin defects. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00618839 (2019).

  55. Centanni, J. M. et al. StrataGraft Skin substitute is well-tolerated and is not acutely immunogenic in patients with traumatic wounds: results from a prospective, randomized, controlled dose escalation trial. Ann. Surg. 253, 672 (2011).

    Article  Google Scholar 

  56. US National Library of Medicine. StrataGraft® skin tissue as an alternative to autografting deep partial-thickness burns. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01437852 (2019).

  57. US National Library of Medicine. StrataGraft® skin tissue as an alternative to autografting full-thickness complex skin defects. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03005054 (2016).

  58. Gibson, A. L. F. et al. A phase 3, open-label, controlled, randomized, multicenter trial evaluating the efficacy and safety of StrataGraft® construct in patients with deep partial-thickness thermal burns. Burns 47, 1024–1037 (2021).

    Article  Google Scholar 

  59. US National Library of Medicine. StrataGraft skin tissue expanded access at specific study sites (StrataCAT). ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04123548 (2021).

  60. US National Library of Medicine. Scarring in stratagraft-treated vs. autograft-treated burn wounds: a clinical and histological investigation. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04896346 (2022).

  61. US National Library of Medicine. StrataGraft safety, tolerability and efficacy in pediatric subjects (StrataSTEPS). ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05517902 (2023).

  62. US National Library of Medicine. StrataGraft overlay of meshed autograft in full-thickness thermal Burns (StrataSOMA). ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04765202 (2023).

  63. Russell, S. et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet 390, 849–860 (2017).

    Article  Google Scholar 

  64. Walsh, C. E. & Batt, K. M. Hemophilia clinical gene therapy: brief review. Transl. Res. 161, 307–312 (2013).

    Article  Google Scholar 

  65. US National Library of Medicine. Gene transfer clinical trial for spinal muscular atrophy type 1. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02122952 (2022).

  66. Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017).

    Article  Google Scholar 

  67. US National Library of Medicine. Study evaluating the safety and pharmacokinetics of JCAR017 in B-cell non-Hodgkin lymphoma (TRANSCEND-NHL-001). ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02631044 (2023).

  68. Anderson, D. E., Gridley, A. & Crawford, D. C. Next generation cartilage repair and the pre-arthroplasty patient. Oper. Tech. Sports Med. 30, 150956 (2022).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank S. Heimann for assistance with database searches of regenerative-medicine companies. The authors acknowledge funding support from the NIH through grants R01DE015038, R01AR071457 and R01AR078389.

Author information

Authors and Affiliations

Authors

Contributions

T.T. conceived the idea for this Review and contributed to researching the data and literature, discussion, writing and editing. R.P.D. and R.C.N. contributed to researching the data and literature, discussion, writing and editing of this manuscript. J.C.H. contributed to the discussion, reviewing and editing of the manuscript. S.C.C. and K.A.A. conceived the idea for this Review and contributed to the discussion, reviewing and editing of the manuscript.

Corresponding author

Correspondence to Kyriacos A. Athanasiou.

Ethics declarations

Competing interests

R.P.D., J.C.H. and K.A.A. are cofounders of and hold equity in Cartilage Inc. The remaining authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Bioengineering thanks István Hornyák, Helen Yu and John Blaho for their contribution to the peer review of this work.

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9/22/2020 (MDR-101): https://www.medeortx.com/news/pr-2020-09-22.php

9/23/2020 (MultiStem): https://www.athersys.com/investors/press-releases/press-release-details/2020/FDA-Grants-RMAT-Designation-to-MultiStem-Cell-Therapy-for-the-Treatment-of-Acute-Respiratory-Distress-Syndrome/default.aspx

10/14/2020 (Orca-T): https://www.globenewswire.com/news-release/2020/10/14/2108307/0/en/Orca-Bio-Receives-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-Orca-T.html

11/11/2020 (AB205): https://angiocrinebioscience.com/news-events/news/

12/17/2020 (AMDC-USR): https://www.biospace.com/article/fda-grants-rmat-designation-for-cook-myosite-s-investigational-autologous-muscle-derived-cells-for-urinary-sphincter-repair/

1/11/2021 (ReNu): https://organogenesis.com/news-events/press-release-01112021.html

3/8/2021 (valoctocogene roxaparvovec): https://investors.biomarin.com/2021-03-08-BioMarin-Announces-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-Granted-to-Valoctocogene-Roxaparvovec-Investigational-Gene-Therapy-for-Hemophilia-A

3/9/2021 (RP-L201): https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-0/

4/21/2021 (ALLO-715): https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-fda-regenerative-medicine/

Oct 2021 (REACT): https://investors.prokidney.com/news-releases/news-release-details/prokidney-corroborates-mechanism-action-reacttm-cell-marker

11/22/2021 (CTX110): http://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-announces-fda-regenerative-medicine-advanced/

12/13/2021 (FT516): https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-positive-durability-response-data

2022 SPAC merger (UD): https://medcitynews.com/2022/01/regenerative-med-biotech-prokidney-inks-825m-merger-to-back-ckd-cell-therapy/

1/5/2022 (Posoleucel): https://ir.allovir.com/news-releases/news-release-details/fda-grants-regenerative-medicine-advanced-therapy-rmat/

1/10/2022 (CT041): https://www.prnewswire.com/news-releases/carsgen-announces-ct041-car-t-cell-product-candidate-granted-rmat-designation-by-the-fda-301456859.html

1/12/2022 (C-CAR039): https://www.cellbiomedgroup.com/newsroom/fda-rmat?lang=en

2/14/2022 (AProArt): https://www.ucsf.edu/news/2022/02/422276/ucsf-gene-therapy-deadly-mutation-fast-tracked-fda-review

4/12/2022 (Exoflo): https://directbiologics.com/fda-grants-direct-biologics-regenerative-medicine-advanced-therapy-rmat-designation-for-the-use-of-exoflo-in-covid-19-related-ards/

4/20/2022 (Posoleucel): https://ir.allovir.com/news-releases/news-release-details/fda-grants-regenerative-medicine-advanced-therapy-rmat-0/

4/25/2022 (Obe-cel): https://autolus.gcs-web.com/news-releases/news-release-details/fda-grants-regenerative-medicine-advanced-therapy-rmat/

5/13/2022 (SkinTE): https://www.prnewswire.com/news-releases/polarityte-announces-fda-regenerative-medicine-advanced-therapy-designation-granted-to-skinte-301546677.html

5/24/2022 (NeoCart): https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-new-cell-therapy-program-following-fda/

6/8/2022 (ALLO-501A): https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-fda-granted-regenerative/

9/28/2022 (CTX130): https://crisprtx.com/about-us/press-releases-and-presentations/crispr-therapeutics-announces-fda-regenerative-medicine-advanced-therapy-rmat-designation-granted-to-ctx130-for-the-treatment-of-cutaneous-t-cell-lymphomas-ctcl

11/8/2022 (ADP-A2M4CD8): https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/234/adaptimmune-reports-increased-response-rate-and-durability

11/29/2022 (CB-010): https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-granted-regenerative-medicine/

1/26/2023 (rebonuputemcel): https://www.discgenics.com/news-posts/2023/1/26/discgenics-announces-fda-regenerative-medicine-advanced-therapy-rmat-designation-granted-to-idct-for-degenerative-disc-disease

2/7/2023 (RP-A501): https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-1/

2/8/2023 (rexlemestrocel-L): https://www.globenewswire.com/en/news-release/2023/02/08/2604535/0/en/FDA-Grants-Regenerative-Medicine-Advanced-Therapy-Rmat-Designation-for-Rexlemestrocel-L-in-Chronic-Low-Back-Pain.html

2/11/2023 (CT103A): https://www.iasobio.com/phone/info.php?id=215

3/21/2023 (NTLA-2002): https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-fda-regenerative-medicine

5/4/2023 (HAV): https://www.globenewswire.com/news-release/2023/05/04/2661452/0/en/Humacyte-s-Human-Acellular-Vessel-HAV-Receives-FDA-s-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-Urgent-Arterial-Repair-Following-Vascular-Trauma.html

5/23/2023 (RP-L301): https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-2/

5/24/2023 (RGX-121): https://www.prnewswire.com/news-releases/regenxbio-receives-fda-regenerative-medicine-advanced-therapy-rmat-designation-for-rgx-121-gene-therapy-for-hunter-syndrome-301831944.html

1997 (US$20 M): https://investors.vcel.com/node/11886/html

1999 (US$58 M): https://www.bioworld.com/articles/392839-biomarin-completes-58m-ipo-as-first-product-nears-market?v=preview

2004 (US$21 M): https://www.intelligentinvestor.com.au/shares/asx-msb/mesoblast-limited/float

2007 (US$56 M): https://www.pehub.com/tigenix-ipo-prices-in-brussels/

2007 Reverse merger (UD): https://www.cleveland.com/business/2007/06/athersys_goes_public_in_revers.html

2008 (UD): https://roic.ai/company/IOVA

2008 Reverse merger (UD): https://www.biospace.com/article/mimedx-announces-post-split-name-change-/

2011 Reverse merger (UD): https://www.cfodive.com/news/reverse-merger-helped-recession-hit-axogen-regain-footing/602531/

2013 (SEK 21 M): https://www.marketscreener.com/quote/stock/MENDUS-AB-PUBL-17946401/news/Immunicum-AB-has-completed-an-IPO-in-the-amount-of-SEK-21-40-million-39111826/

2013 (US$116 M): https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-closing-initial-public-offering-and

2013 (US$40 M): https://www.fiercebiotech.com/r-d/fate-ipo-flop-raises-fresh-concerns-about-investors-appetite-for-biotech

2013 Reverse merger (UD): https://www.biospace.com/article/china-s-b-cellular-biomedicine-group-b-announces-reverse-merger-/

2013 Reverse merger (UD): https://www.businesswire.com/news/home/20131121005377/en/Capricor-and-Nile-Therapeutics-Complete-Merger-to-Form-Capricor-Therapeutics-Inc.

2014 (US$265 M): https://www.fiercebiotech.com/r-d/updated-juno-banks-a-265m-ipo-pushing-next-big-thing-oncology

2015 (US$124 M): https://www.businesswire.com/news/home/20150408005269/en/SanBio-Announces-Pricing-of-Initial-Public-Offering-on-Tokyo-Stock-Exchange

2015 (US$159 M): https://www.globenewswire.com/news-release/2015/09/22/770163/10150220/en/REGENXBIO-Announces-Closing-of-Initial-Public-Offering-and-Full-Exercise-of-Underwriters-Option-to-Purchase-Additional-Shares.html

2015 (US$191 M): https://www.nasdaq.com/articles/adaptimmune-therapeutics-prices-upsized-ipo-17-high-end-range-2015-05-05

2015 (US$36 M): https://www.fiercebiotech.com/r-d/kiadis-banks-36m-a-euro-ipo-to-fund-its-stem-cell-r-d

2015 (US$5.5 M): https://www.prnewswire.com/news-releases/asterias-biotherapeutics-completes-public-offering-and-private-placement-of-common-stock-300033976.html

2015 (US$81 M): https://ir.voyagertherapeutics.com/news-releases/news-release-details/voyager-therapeutics-announces-closing-initial-public-offering/

2016 (US$113 M): https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-closing-initial-public-offering

2016 (US$56 M): https://www.fiercebiotech.com/biotech/crispr-therapeutics-raises-a-56m-ipo-but-patent-battles-potential-stock-drops-loom

2016 (US$75 M): https://pitchbook.com/newsletter/audentes-raises-75m-in-ipo

2016 Acquired by Mallinckrodt (UD): https://www.fiercebiotech.com/medical-devices/mallinckrodt-acquires-regenerative-medicine-company-stratatech

2017 (US$46 M): https://www.globenewswire.com/en/news-release/2017/09/22/1131592/0/en/Krystal-Biotech-Announces-Closing-of-Initial-Public-Offering-and-Full-Exercise-of-Underwriters-Option-to-Purchase-Additional-Shares.html

2017 (US$77 M): https://www.globenewswire.com/en/news-release/2017/10/02/1139020/0/en/Nightstar-Announces-Closing-of-Initial-Public-Offering-and-Full-Exercise-of-Underwriters-Option-to-Purchase-Additional-American-Depositary-Shares.html

2017 Reverse merger (UD): https://www.globenewswire.com/news-release/2017/04/07/1052850/0/en/PolarityTE-TM-Inc-Announces-Completion-of-Merger-and-Acquires-Important-Intellectual-Property-for-Regenerative-Medicine-Programs.html

2018 (US$100 M): https://www.businesswire.com/news/home/20180625006210/en/Magenta-Therapeutics-Announces-Closing-of-Initial-Public-Offering

2018 (US$160 M): https://autolus.gcs-web.com/news-releases/news-release-details/autolus-announces-closing-initial-public-offering-and-full/

2018 (US$225 M): https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-closing-225-million-initial/

2018 (US$373 M): https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-closing-initial-public-offering/

2018 Acquired by Celgene (US$9,000 M): https://www.geekwire.com/2018/juno-therapeutics-acquired-celgene-9b-dramatic-deal-rising-biotech-star/

2018 Acquired by Takeda Pharmaceutical Company (US$608 M): https://www.pharmaceutical-technology.com/news/takeda-tigenix-acquisition-608m/

2018 Reverse merger (UD): https://endpts.com/gene-therapy-startup-rocket-pharma-reverse-merges-with-troubled-inotek-after-25m-raise/

2018 Reverse merger (UD): https://organogenesis.com/news-events/press-release-12102018.html

2019 Acquired by Biogen (US$800 M): https://investors.biogen.com/news-releases/news-release-details/biogen-completes-acquisition-nightstar-therapeutics

2019 Acquired by BioTime (UD): https://www.spglobal.com/marketintelligence/en/news-insights/trending/dgy96s7WowE7oCnW-Mu7KA2

2019 Acquired by Castle Creek Pharmaceutical (US$63 M): https://www.globenewswire.com/en/news-release/2019/09/12/1915187/33272/en/Castle-Creek-Pharmaceutical-Holdings-to-Acquire-Fibrocell.html

2019 Acquired by Sumitomo Dainippon Pharma (UD): https://enzyvant.com/sumitomo-dainippon-pharma-completes-the-formation-of-the-strategic-alliance-with-roivant-sciences/

2019 Reverse merger (UD): https://www.nbcphiladelphia.com/news/local/malvern-gene-therapy-company-completes-reverse-merger/219782/

2020 (US$224 M): https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-announces-pricing-initial-public-offering/

2020 (US$318 M): https://www.globenewswire.com/en/news-release/2020/08/03/2072010/0/en/AlloVir-Announces-Closing-of-Upsized-Initial-Public-Offering-and-Full-Exercise-of-the-Underwriters-Option-to-Purchase-Additional-Shares.html

2020 Acquired by Astellas Pharma (US$3,000 M): https://www.spglobal.com/marketintelligence/en/news-insights/trending/VpqpVltOd5YKifSvTvBf2A2

2021 (US$150 M): https://ir.talaristx.com/news-releases/news-release-details/talaris-therapeutics-announces-closing-initial-public-offering/

2021 (US$304 M): https://www.businesswire.com/news/home/20210727006010/en/Caribou-Biosciences-Announces-Closing-of-Upsized-Initial-Public-Offering

2021 (US$400 M): https://www.bioworld.com/articles/508424-car-t-developer-carsgen-debuts-on-hkex-with-400m-ipo-targets-bcma-first?v=preview

2021 Acquired by consortium (US$411 M): https://www.prnewswire.com/news-releases/cellular-biomedicine-group-inc-announces-completion-of-merger-301231873.html

2021 Acquired by Sanofi (US$358 M): https://www.fiercebiotech.com/biotech/sanofi-inks-358m-kiadis-takeover-to-acquire-nk-cell-platform

2021 Reverse merger (UD): https://www.marketscreener.com/quote/stock/HUMACYTE-INC-126300449/news/Humacyte-Inc-completed-the-acquisition-of-Alpha-Healthcare-Acquisition-Corp-from-a-group-of-share-36263997/

2022 Acquired by Canaria Bio (UD): https://www.koreabiomed.com/news/articleView.html?idxno=20085

2022 Merger with Cend Therapeutics (UD): https://www.globenewswire.com/en/news-release/2022/09/15/2516989/18623/en/Caladrius-Biosciences-and-Cend-Therapeutics-Announce-Closing-of-Merger-and-the-Emergence-of-Lisata-Therapeutics.html

20 cellular and gene therapy products: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products

21 CFR 312: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=312

525 non-regenerative-medicine drugs: https://www.fda.gov/drugs/development-approval-process-drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products

7% in bank fees for a US$100 million IPO: https://news.crunchbase.com/public/want-to-take-your-startup-public-heres-what-it-actually-costs-to-ipo/

86 RMAT designations: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/cumulative-cber-regenerative-medicine-advanced-therapy-rmat-designation-requests-received-fiscal

a list and ranking of incubators and accelerators worldwide: https://www.andeglobal.org/publication/the-ubi-global-world-rankings-of-business-incubators-and-accelerators/

a US$20 million award from the California Institute for Regenerative Medicine (CIRM): https://www.fiercebiotech.com/biotech/stemcells-inc-awarded-20-million-from-california-institute-for-regenerative-medicine-for

Abecma (2021): https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-multiple-myeloma

Accelerators: https://www.feedough.com/accelerator-vs-incubator/

acquired by Celgene: https://www.geekwire.com/2018/juno-therapeutics-acquired-celgene-9b-dramatic-deal-rising-biotech-star/

acquired by Mallinckrodt Pharmaceuticals: https://www.fiercebiotech.com/medical-devices/mallinckrodt-acquires-regenerative-medicine-company-stratatech

acquired by Novartis: https://www.novartis.com/news/media-releases/novartis-enters-agreement-acquire-avexis-inc-usd-87-bn-transform-care-sma-and-expand-position-gene-therapy-and-neuroscience-leader

acquired in a reverse merger: https://www.businesswire.com/news/home/20190930005241/en/Ocugen-Announces-Completion-of-its-Merger-with-Histogenics-to-Create-Nasdaq-Listed-Clinical-Stage-Company-Developing-Novel-Ocular-Gene-Therapies-and-Biotherapeutics

acquired through a reverse merger: https://www.massdevice.com/stemcells-soars-on-reverse-merger-with-israels-microbot-medical/

Adstiladrin (2022): https://www.ferring.com/ferring-receives-approval-from-u-s-fda-for-adstiladrin-for-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/

Amgen: https://sciencebusiness.net/news/74714/UCL-spin-out-sold-to-Amgen-in-%241-billion-deal

amount for a seed round: https://www.paddle.com/resources/guide-to-seed-funding-for-startups

Analysts consider: https://www.statnews.com/2016/06/01/stem-cell-company-shutters

approved as Breyanzi: https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-a-New-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx

approved as Rethymic): https://endpts.com/after-three-decades-and-a-surprise-rejection-first-treatment-for-babies-born-without-a-thymus-secures-fda-approval/

approved by the US Food and Drug Administration: https://www.fda.gov/vaccines-blood-biologics/zolgensma

approved: https://www.fda.gov/vaccines-blood-biologics/stratagraft

AProArt: https://www.cirm.ca.gov/our-progress/awards/ex-vivo-transduction-human-artemis-dclre1c-cdna-lentiviral-vector-aproart-cd34

ATIR101: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/allodepleted-t-cell-immunotherapeutic-atir101

averages for VC series A, B, and C: https://www.evaluate.com/vantage/articles/insights/venture-financing-ipo/venture-financing-holds-steady-device-makers

AveXis: https://www.novartis.com/news/media-releases/novartis-enters-agreement-acquire-avexis-inc-usd-87-bn-transform-care-sma-and-expand-position-gene-therapy-and-neuroscience-leader

Baylor College of Medicine: https://elevate.bio/press-releases/elevatebio-announces-that-allovir-joins-its-portfolio-of-highly-innovative-cell-and-gene-therapy-companies/; https://www.tessacell.com/about-tessa-therapeutics/

BioVex: https://mergr.com/amgen-acquires-biovex-group

BLA clinical review: https://www.fda.gov/vaccines-blood-biologics/stratagraft

BLA pharmacology/toxicology review of StrataGraft: https://www.fda.gov/vaccines-blood-biologics/stratagraft

Bluebird Bio (founded as Genetix Pharmaceuticals): https://investor.bluebirdbio.com/news-releases/news-release-details/genetix-pharmaceuticals-renamed-bluebird-bio-announces

Breyanzi (2021): https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-a-New-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx

California Institute for Regenerative Medicine (CIRM): https://www.cirm.ca.gov/

cartilage repair products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/preparation-ides-and-inds-products-intended-repair-or-replace-knee-cartilage

Carvykti (2022): https://www.jnj.com/u-s-fda-approves-carvykti-ciltacabtagene-autoleucel-janssens-first-cell-therapy-a-bcma-directed-car-t-immunotherapy-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma

Case Western Reserve University: https://case.edu/medicine/about/newsroom/our-latest-news/case-western-reserve-center-stem-cell-and-regenerative-medicine-and-athersys-receive-1m-third-frontier-grant-support-research-spinal-cord-injury

cellular immunotherapy product Provenge: https://stanmed.stanford.edu/pioneering-cancer-drug-provenge-fresh-look

CFR Title 21: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm

CGT products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/preclinical-assessment-investigational-cellular-and-gene-therapy-products

Children’s Hospital of Philadelphia University of Pennsylvania: https://www.chop.edu/news/childrens-hospital-philadelphia-celebrates-fda-approval-gene-therapy-inherited-blindness

City of Hope National Medical Center: https://www.cityofhope.org/news/phase-1-clinical-trial-of-mb-101

clinical trials: https://www.fda.gov/patients/clinical-trials-what-patients-need-know/what-are-different-types-clinical-research

completed an initial public offering (IPO): https://www.globenewswire.com/en/news-release/2016/02/11/809635/0/en/AveXis-Announces-Pricing-of-Initial-Public-Offering.html

considered safety data generated from the phase I/IIa and phase II trials for an alternate indication: https://www.fda.gov/vaccines-blood-biologics/stratagraft

convertible note: https://www.investopedia.com/terms/s/senior-convertible-note.asp

Cooperative Patent Classification system: https://www.cooperativepatentclassification.org/about

current Good Manufacturing Practice (cGMP) regulations: https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations

Dilution of equity: https://www.svb.com/startup-insights/startup-equity/startup-equity-dilution

Duke University, Massachusetts Institute of Technology: https://wraltechwire.com/2021/02/18/a-blooming-success-the-rise-of-humacyte-from-humble-beginnings-to-1-1b-valuation/

Duke University: https://endpts.com/after-three-decades-and-a-surprise-rejection-first-treatment-for-babies-born-without-a-thymus-secures-fda-approval/

Duke University: https://endpts.com/after-three-decades-and-a-surprise-rejection-first-treatment-for-babies-born-without-a-thymus-secures-fda-approval/

‘End of Phase’ meetings: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-ind-milestone-type-b-meetings

Enzyvant Therapeutics GmbH licenced the technology from Duke University: https://www.prnewswire.com/news-releases/enzyvant-to-develop-novel-biologic-therapy-for-complete-digeorge-syndrome-300386922.html

established IP: https://patents.justia.com/assignee/histogenics-corporation

exceeding US$20 billion in 2021: https://alliancerm.org/sector-report/2021-annual-report/

excess of these amounts: https://grants.nih.gov/grants/guide/notice-files/NOT-HL-22-065.html

FDA approval of JCAR017: https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-a-New-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx

Ferring Pharmaceuticals: https://ferringusa.com/?press=ferring-and-blackstone-life-sciences-invest-over-570-million-usd-in-novel-gene-therapy-for-bladder-cancer-patients

Financial exit strategies: https://www.investopedia.com/terms/b/business-exit-strategy.asp

founded in 2013: https://www.prnewswire.com/news-releases/spark-therapeutics-launched-with-50-million-in-financing-to-advance-late-and-mid-stage-gene-therapy-programs-with-clinical-proof-of-concept-228752221.html

Fred Hutchinson Cancer Center, St Jude Children’s Research Hospital: https://ir.mustangbio.com/news-events/press-releases/detail/68/mustang-bio-and-st-jude-childrens-research-hospital

Fred Hutchinson Cancer Research Center Memorial Sloan-Kettering Cancer Center Seattle Children’s Research Institute: https://www.forbes.com/sites/matthewherper/2014/08/05/why-this-cancer-fighting-company-has-raised-300-million-in-just-12-months/

Fred Hutchinson Cancer Research Center Memorial Sloan-Kettering Cancer Center Seattle Children’s Research Institute University of California, San Francisco St Jude Children’s Research Hospital: https://www.businesswire.com/news/home/20171101006552/en/Juno-Therapeutics-Reports-Third-Quarter-2017-Financial-Results

funding caps: https://www.sbir.gov/about

Genesis Seed Fund: https://research.rutgers.edu/researcher-support/commercialize-your-innovation/launch-startup/new-ventures/genesis-seed-fund

Gilead Sciences: https://www.gilead.com/news-and-press/company-statements/kite-pharma

Harvard University, Massachusetts Institute of Technology: https://news.mit.edu/2001/sicklecell

Harvard University, Washington University in St Louis, Stanford University, San Raffaele Telethon Institute for Gene Therapy, University of Basel: https://investor.magentatx.com/news-releases/news-release-details/magenta-therapeutics-announces-485m-series-financing-transform/

Harvard University: https://hsci.harvard.edu/company-startups

Harvard University: https://hsci.harvard.edu/company-startups

Hemgenix (2022): https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b

highly competitive: https://grantengine.com/sbir-sttr-paylines-by-nih-institute/

Imlygic (2015): https://www.amgen.com/newsroom/press-releases/2015/10/fda-approves-imlygic-talimogene-laherparepvec-as-first-oncolytic-viral-therapy-in-the-us

INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-interact-meeting

interpretations of Section 506(g)(8) by the US Food and Drug Administration (FDA): https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/resources-related-regenerative-medicine-therapies

‘inventive step’: https://www.wipo.int/pct/en/texts/ispe/13_01_02.html

Investigational New Drug application: https://www.fda.gov/vaccines-blood-biologics/stratagraft

IPO: https://pitchbook.com/blog/ipo-process-explained

JLABS: https://jnjinnovation.com/home

Johns Hopkins University: https://www.sdbj.com/technology/capricor-therapeutics-relocates-la-jolla/

Johnson & Johnson: https://johnsonandjohnson.gcs-web.com/news-releases/news-release-details/johnson-johnson-announces-completion-merger-centocor-inc/

Juno Therapeutics (founded as FC Therapeutics): https://pitchbook.com/profiles/company/60580-27#overview

Juno Therapeutics: https://www.geekwire.com/2018/juno-therapeutics-acquired-celgene-9b-dramatic-deal-rising-biotech-star/

Katholieke Universiteit Leuven Ghent University: https://www.flandersinvestmentandtrade.com/invest/en/news/tigenix-raise-20-million-euro-product-trials

Kymriah (2017): https://www.novartis.com/news/media-releases/novartis-receives-first-ever-fda-approval-car-t-cell-therapy-kymriahtm-ctl019-children-and-young-adults-b-cell-all-refractory-or-has-relapsed-least-twice

Kymriah: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/kymriah-tisagenlecleucel

Luxturna (2017): https://sparktx.com/press_releases/fda-approves-spark-therapeutics-luxturna-voretigene-neparvovec-rzyl-a-one-time-gene-therapy-for-patients-with-confirmed-biallelic-rpe65-mutation-associated-retinal-dystrophy/

Luxturna to be approved by the US Food and Drug Administration: https://sparktx.com/press_releases/fda-approves-spark-therapeutics-luxturna-voretigene-neparvovec-rzyl-a-one-time-gene-therapy-for-patients-with-confirmed-biallelic-rpe65-mutation-associated-retinal-dystrophy/

M&A: https://www.sba.gov/business-guide/grow-your-business/merge-acquire-businesses

MACI (2016): https://investors.vcel.com/news-releases/news-release-details/fda-approves-maci-treatment-symptomatic-cartilage-defects-knee

Mallinckrodt Pharmaceuticals: https://mallinckrodt.gcs-web.com/news-releases/news-release-details/mallinckrodt-announces-us-fda-approval-stratagraftr-allogeneic/

Massachusetts Institute of Technology: https://organogenesis.com/about-us/

Massachusetts Institute of Technology: https://organogenesis.com/about-us/

MGTA-456: https://investor.magentatx.com/news-releases/news-release-details/magenta-therapeutics-announces-updated-phase-2-data-mgta-456/

National Cancer Institute: https://www.stocktitan.net/news/IOVA/iovance-biotherapeutics-announces-first-patient-randomized-in-phase-1fnhlejx69wn.html

Nationwide Children’s Hospital Ohio State University: https://www.nationwidechildrens.org/newsroom/news-releases/2013/10/avexis-biolife-licenses-spinal-muscular-atrophy-sma-patent-portfolio-from-nationwide-childrens

Nationwide Children’s Hospital: https://www.prnewswire.com/news-releases/abeona-therapeutics-and-nationwide-childrens-hospital-receive-prestigious-global-genes-champions-of-hope-award-for-patient-advocacy-227092241.html

NIH Data Management and Sharing Policy: https://oir.nih.gov/sourcebook/intramural-program-oversight/intramural-data-sharing/2023-nih-data-management-sharing-policy

NIH’s Commercialization Readiness Pilot (CRP) programme: https://seed.nih.gov/support-for-small-businesses/commercialization-enhancement-programs/crp

no major safety concerns were generated from the preclinical studies: https://www.fda.gov/vaccines-blood-biologics/stratagraft

NSF-funded Innovation-Corps (I-Corps): https://beta.nsf.gov/funding/initiatives/i-corps/about-i-corps

obtained Regenerative Medicine Advanced Therapy designation: https://www.prnewswire.com/news-releases/us-fda-designates-mallinckrodts-stratagraft-as-regenerative-medicine-advanced-therapy-300489200.html

only the phase Ib and phase III trials were considered for efficacy: https://www.fda.gov/vaccines-blood-biologics/stratagraft

Orca-T: https://ashpublications.org/blood/article/140/Supplement1/654/487614/Precision-Engineered-Cell-Therapy-Orca-T

OTL-103: https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-fda-regenerative-medicine/

over 1,000 new devices: https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-reports

University of Oxford, University of Pennsylvania: https://www.adaptimmune.com/our-company

Patent Cooperation Treaty (PCT): https://www.wipo.int/pct/en/faqs/faqs.html

peak sales forecast: https://www.europeanpharmaceuticalreview.com/news/179320/cd19-car-t-agents-to-boost-blood-cancer-market/

Phase 0 grants: https://www.sbir.gov/sites/default/files/SBIR-Table_StateMatchingPhase0_Sept2020.pdf

pledged a US$50 million commitment from the Children’s Hospital of Philadelphia: https://www.prnewswire.com/news-releases/spark-therapeutics-launched-with-50-million-in-financing-to-advance-late-and-mid-stage-gene-therapy-programs-with-clinical-proof-of-concept-228752221.html

pre-IND meeting: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-pre-ind-meetings

private equity (PE): https://www.investopedia.com/terms/p/privateequity.asp

product revenue of Breyanzi: https://bioprocessintl.com/bioprocess-insider/therapeutic-class/bms-sees-car-t-sales-rocket-in-line-with-increased-capacity/

Promotion and Tenure-Innovation and Entrepreneurship (PTIE) coalition: https://ptie.org/

Provenge (2010): https://stanmed.stanford.edu/pioneering-cancer-drug-provenge-fresh-look/

quality management system: https://www.nidcr.nih.gov/sites/default/files/2017-12/quality-management-of-clinical-research-brief-overview.doc

raised a total of US$310 million: https://www.crunchbase.com/organization/juno-therapeutics/company_financials

raised an additional US$72.8 million in series B funding: https://www.prnewswire.com/news-releases/spark-therapeutics-raises-728-million-in-oversubscribed-financing-260806381.html

raised US$304 million through its initial public offering: https://www.nasdaq.com/articles/juno-therapeutics-prices-upsized-ipo-24-largest-2014-biotech-ipo-22-billion-market-cap

reason for noncompliance: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1

Regenerative Medicine Advanced Therapy (RMAT) designation: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation

Regenerative Medicine Minnesota: https://www.regenmedmn.org/

Rethymic (2021): https://enzyvant.com/enzyvant-receives-fda-approval-for-rethymic-allogeneic-processed-thymus-tissue-agdc-a-one-time-regenerative-tissue-based-therapy-for-pediatric-congenital-athymia/

reverse merger: https://www.investopedia.com/terms/r/reversetakeover.asp

Rexlemestrocel-L: https://go.drugbank.com/drugs/DB17606

Risk Evaluation and Mitigation Strategy programme: https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems

Roche: https://technical.ly/startups/spark-therapeutics-acquired-roche-bill-marrazzo-university-city-science-center-gene-therapy/

Roughly 90% of applications filed are utility patents: https://www.uspto.gov/web/offices/ac/ido/oeip/taf/data/patdesc.htm

San Raffaele-Telethon Institute for Gene Therapy: https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-fda-regenerative-medicine/

SBA loans: https://www.sba.gov/funding-programs/loans

SBIR and STTR programmes: https://www.sbir.gov/node/2120519

secondary public offerings: https://www.cbinsights.com/research-what-is-a-secondary-offering

section 361: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271

Section 506(g)(8) of the United States (US) Federal Food, Drug, and Cosmetic Act: https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.htm

Seoul National University: https://www.koreabiomed.com/news/articleView.html?idxno=20085

settled a legal dispute: https://www.wsj.com/articles/juno-therapeutics-settles-patent-dispute-with-novartis-1428326691

Several expedited programmes: https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review

SkinTE: https://www.woundsource.com/product/skinte

Skysona (2022): https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-receives-fda-accelerated-approval-skysonar-gene

Spark Therapeutics: https://sparktx.com/press_releases/spark-therapeutics-enters-into-definitive-merger-agreement-with-roche/

Stanford University: https://orcabio.com/who-we-are/

Stanford University: https://www.medeortx.com/about-us.php

StrataGraft (2021): https://mallinckrodt.gcs-web.com/news-releases/news-release-details/mallinckrodt-announces-us-fda-approval-stratagraftr-allogeneic/

StrataGraft: https://www.stratagraft.com/

Stratatech: https://www.fiercebiotech.com/medical-devices/mallinckrodt-acquires-regenerative-medicine-company-stratatech

subsequently approved: https://www.ns-healthcare.com/news/breyanzi-large-b-cell-lymphoma/

Sumitomo Pharma: https://endpts.com/after-three-decades-and-a-surprise-rejection-first-treatment-for-babies-born-without-a-thymus-secures-fda-approval/

Tecartus (2020): https://www.gilead.com/news-and-press/press-room/press-releases/2020/7/us-fda-approves-kites-tecartus-the-first-and-only-car-t-treatment-for-relapsed-or-refractory-mantle-cell-lymphoma

technology for Brenyanzi: https://www.forbes.com/sites/matthewherper/2014/08/05/why-this-cancer-fighting-company-has-raised-300-million-in-just-12-months/?sh=449f6d8b50d5

technology for StrataGraft: https://pathology.wisc.edu/2021/06/21/stratagraft-approved-by-fda/

technology of Zolgensma: https://www.nationwidechildrens.org/newsroom/news-releases/2013/10/avexis-biolife-licenses-spinal-muscular-atrophy-sma-patent-portfolio-from-nationwide-childrens

three FDA-approved products: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/cber-regenerative-medicine-advanced-therapy-rmat-approvals

three types of patent: https://www.uspto.gov/patents/basics/general-information-patents

“treat, modify, reverse, or cure a serious or life-threatening condition”: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation

TT11: https://www.tessacell.com/pipeline/

UniQure (founded as Amsterdam Molecular Therapeutics): https://www.biopharmadive.com/news/hemophilia-gene-therapy-fda-approval-hemgenix-csl-uniqure/636999/

Université de Montréal University of Toronto: https://www.signalsblog.ca/catching-up-with-excellthera-and-co-founder-guy-sauvageau/

University College London: https://www.uclb.com/portfolio/our-spinouts/orchard-theapeutics-plc/

University of California San Diego (UCSD): https://innovation.ucsd.edu/commercialize/licensing.html

University of California, Berkeley: https://ipira.berkeley.edu/caribou-biosciences-inc

University of California, Berkeley: https://ipira.berkeley.edu/intellia

University of California, Irvine: https://innovation.uci.edu/2016/11/20161129special-feature-stem-cell-strides-asterias-biotherapeutics/

University of California, Irvine: https://innovation.uci.edu/2020/06/uci-startup-company-jcyte-partners-with-santen-pharmaceutical/

University of California, Los Angeles: https://labusinessjournal.com/news/arie-belldegrun/

University of California, Los Angeles: https://www.biopharmadive.com/news/Kite-Pharma-UCLA-tcell-allogeneic/423263/

University of California, San Francisco: https://www.ucsf.edu/news/2022/02/422276/ucsf-gene-therapy-deadly-mutation-fast-tracked-fda-review

University College London: https://www.autolus.com/about-us/

University of Colorado University of Illinois at Chicago: https://www.fiercebiotech.com/biotech/eye-specialist-ocugen-looks-east-for-second-round-fundraising

University of Eastern Finland: https://www.uef.fi/en/article/university-of-eastern-finland-and-ferring-ventures-to-continue-collaboration-in-gene-and-cell

University of Florida: https://ir.axogeninc.com/press-releases/detail/811/axogen-inc-receives-david-j-gury-company-of-the-year

University of Florida: https://news.drgator.ufl.edu/2013/09/26/uf-teams-with-company-to-advance-gene-therapy-treatments/

University of Louisville: https://www.uoflnews.com/post/uofltoday/uofl-born-company-secures-100-million-to-advance-cell-therapy/

University of Massachusetts University of California, San Francisco Stanford University: https://www.umassmed.edu/es/news/news-archives/2014/02/voyager-therapeutics-targets-novel-gene-therapies-to-combat-diseases/

University of Minnesota: https://www.nytimes.com/2002/12/11/business/technology-politically-correct-stem-cell-is-licensed-to-biotech-concern.html

University of Oxford: https://www.ox.ac.uk/news/2015-11-09-£23-million-boost-oxford-spinout-company

University of Pennsylvania: https://pci.upenn.edu/regenxbio-receives-fda-fast-track-designation-for-its-novel-gene-therapy-candidate/

University of Pennsylvania: https://www.novartis.com/news/media-releases/novartis-kymriah-receives-fda-regenerative-medicine-advanced-therapy-designation-follicular-lymphoma

University of Pennsylvania: https://www.pennmedicine.org/news/news-releases/2019/september/university-pennsylvania-announces-exclusive-alliance-novartis-development-new-focused-relationship

University of Washington, Children’s Hospital Boston Mass General Hospital for Children: https://iscrm.uw.edu/fate-therapeutics-a-company-started-in-seattle-with-intellectual-property-from-iscrm-has-announced-its-first-clinical-trials/

University of Wisconsin: https://pathology.wisc.edu/2021/06/21/stratagraft-approved-by-fda/

University of Wisconsin — Madison: https://news.wisc.edu/gov-evers-state-leaders-tour-uw-biotech-spinoff-stratatech/

updated the US policy guidance: https://www.whitehouse.gov/ostp/news-updates/2022/08/25/ostp-issues-guidance-to-make-federally-funded-research-freely-available-without-delay/

US$10 million in series C: https://www.wsj.com/articles/DJFVW00120150109eb19ozrd9

US$13.1 million: https://www.pehub.com/histogenics-adds-131-million/

US$34 million: https://www.massdevice.com/histogenics-raises-34-million-after-prochon-biotech-merger/

US$49 million: https://www.fiercebiotech.com/biotech/histogenics-closes-49-million-series-a-fundraising-to-support-commercial-development-of-0

US$5.35 million: https://www.prweb.com/releases/2008/05/prweb908944.htm/

US$65 million in series D: https://www.fiercebiotech.com/biotech/avexis-secures-65-million-financing

US$65 million through an initial public offering: https://www.bizjournals.com/boston/blog/bioflash/2014/12/with-65m-offering-histogenics-becomes-states-17th.html

US$9.0 million: https://www.fiercebiotech.com/biotech/histogenics-secures-9-million-second-round-of-financing

Vyjuvek (2023): https://www.fda.gov/vaccines-blood-biologics/vyjuvek

Weizmann Institute: https://www.haaretz.com/israel-news/2017-08-31/ty-article/kite-pharmas-success-is-nothing-compared-to-tevas-failure/0000017f-dbae-df9c-a17f-ffbef7f70000

Weill Cornell Medicine: https://angiocrinebioscience.com/about-us/our-story/

Western New York Incubator Network SBIR/STTR assistance programme: https://www.wnyincubators.com/sbir-sttr-assistance

Y Combinator Management: https://www.ycombinator.com/

Yescarta (2017): https://www.gilead.com/news-and-press/press-room/press-releases/2020/7/us-fda-approves-kites-tecartus-the-first-and-only-car-t-treatment-for-relapsed-or-refractory-mantle-cell-lymphoma

Zolgensma (2019): https://www.novartis.com/news/media-releases/avexis-receives-fda-approval-zolgensma-first-and-only-gene-therapy-pediatric-patients-spinal-muscular-atrophy-sma

Zynteglo (2022): https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-fda-approval-zynteglor-first-gene-therapy

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Takahashi, T., Donahue, R.P., Nordberg, R.C. et al. Commercialization of regenerative-medicine therapies. Nat Rev Bioeng 1, 906–929 (2023). https://doi.org/10.1038/s44222-023-00095-9

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