Endocyte

Last updated
Endocyte
Type Subsidiary
Nasdaq: ECYT
Industry Biopharmaceutical
Founded1996 (1996)
Headquarters
West Lafayette, Indiana
,
United States
Key people
Mike Sherman, President and CEO
Number of employees
78
Parent Novartis
Website www.endocyte.com

Endocyte (NASDAQ: ECYT) is a biopharmaceutical company established in 1996 and headquartered in West Lafayette, Indiana, [1] a resident of the Purdue Research Park. [2] In 2011 the company completed successfully an initial public offering (IPO). [3] As of 2013, the company had 93 employees. [1] The original president and CEO, Ron Ellis, [1] was succeeded by Mike Sherman, who held a CFO position at the company before this change in June 2016. In 2018 the company was acquired by Novartis. [4]

Endocyte is advancing the first technology platform for the creation of small molecule drug conjugates (a.k.a. SMDCs), which consist of a small molecule linked to a potent drug, and is developing a pipeline of SMDCs together with non-invasive companion imaging agents for cancer, inflammatory diseases and kidney disease (autosomal-dominant polycystic kidney disease/ADPKDor PKD). [1] [5] Endocyte’s lead drug candidate is vintafolide, an investigational targeted cancer therapeutic in late-stage development. In 2012 marketing rights were acquired by Merck for $120 million in an upfront payment and up to $880 million in milestone payments. [6] Vintafolide is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor, which is expressed on many cancers, such as ovarian cancer, and a potent chemotherapy drug, a derivative of vinblastine. [1] Endocyte retained rights to the development and commercialization of etarfolatide. [6]

Endocyte’s other preclinical drug candidates also target the folate receptor as well as prostate-specific membrane antigen (PSMA) receptors. [1] The company was formed based on technology developed by Philip Low (the company's CSO), and Christopher Leamon, PhD, the company’s VP of research. This technology is a folic acid-based drug delivery system, [1] referred to now as folate targeting. [7] The company is also developing SMDCs with varying drug payloads as well as different ligands for other molecular targets, such as prostate-specific membrane antigen (PSMA) and has also developed, with Bristol-Myers Squibb, an epothilone-folic acid conjugate (BMS-753493), described at a 2008 conference. [8]

In mid-October 2018, Novartis announced it would acquire Endocyte Inc for $2.1 billion ($24 per share) merging it with a newly created subsidiary. [9] [10] Endocyte will bolster Novartis' offering in its radiopharmaceuticals business, with Endocyte's first in class candidate 177Lu-PSMA-617 being targeted against metastatic castration-resistant prostate cancer. [11]

Related Research Articles

Folate Vitamin B9; nutrient essential for DNA synthesis

Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division. As humans cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.

Novartis Swiss multinational pharmaceutical corporation

Novartis International AG is a Swiss multinational pharmaceutical corporation based in Basel, Switzerland. It is one of the largest pharmaceutical companies in the world.

α-Amanitin Chemical compound

α-Amanitin (alpha-Amanitin) is a cyclic peptide of eight amino acids. It is possibly the most deadly of all the amatoxins, toxins found in several species of the mushroom genus Amanita, one being the death cap as well as the destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. It is also found in the mushrooms Galerina marginata and Conocybe filaris. The oral LD50 of amanitin is 100 μg/kg for rats.

Sulfamethoxazole

Sulfamethoxazole is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as Listeria monocytogenes and E. coli.

Chimeric antigen receptor T cells are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy.

Targeted therapy Type of therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

Fluorine-18 Isotope of fluorine emitting a positron

Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time. Both modes of decay yield stable oxygen-18.

A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).

Glutamate carboxypeptidase II

Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

Copper-64 (64Cu) is a positron and beta emitting isotope of copper, with applications for molecular radiotherapy and positron emission tomography. Its unusually long half (12.7-hours) for a positron-emitting isotope makes it increasingly useful when attached to various ligands, for PET and PET-CT scanning.

Folate targeting is a method utilized in biotechnology for drug delivery purposes. This Trojan Horse process, which was created by Drs. Christopher P. Leamon and Philip S. Low, involves the attachment of the vitamin, folate, to a molecule/drug to form a "folate conjugate". Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis. Molecules as diverse as small radiodiagnostic imaging agents to large DNA plasmid formulations have successfully been delivered inside FR-positive cells and tissues.

Vintafolide

Vintafolide is an investigational targeted cancer therapeutic currently under development by Endocyte and Merck & Co. It is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor, which is overexpressed on certain cancers, such as ovarian cancer, and a potent chemotherapy drug, vinblastine.

Small molecule drug conjugates or SMDCs are built with three modules: a targeting ligand, a linker and a drug payload. The targeting ligands consist of low molecular weight, high-affinity ligands that are precisely linked to potent drugs. The linkers are designed to be stable in the bloodstream and then release the active drug from the targeting ligand when the SMDC is taken up by the diseased cell. The drug payloads are highly active molecules that are too toxic to be administered in their untargeted forms at therapeutic dose levels. This modular approach allows varying targeting ligands, linker systems and drug payloads and generate SMDCs for different diseases. The most advanced SMDC is vintafolide, a derivative of the anti-mitotic chemotherapy drug vinblastine which is chemically linked to folic acid. Potent, bioactive natural products like triptolide that inhibit mammalian transcription has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.

Technetium (<sup>99m</sup>Tc) etarfolatide

Technetium (99mTc) etarfolatide is an investigational non-invasive, folate receptor-targeting companion imaging agent that is being developed by Endocyte. Etarfolatide consists of a small molecule targeting the folate receptor and an imaging agent, which is based on technetium-99m. This companion imaging agent identifies cells expressing the folate receptor, including cancer and inflammatory cells.

Advanced Accelerator Applications is a pharmaceutical group specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.


DMTHF-Tc is a radiopharmaceutical which combines DMTHF, a modified folate, with technetium-99m (99mTc), a gamma emitting radionuclide, in a chelate conjugate. It shows selectivity for certain cancer cells which overexpress FR-α, and can therefore be used for diagnostic imaging in nuclear medicine. DMTHF-Tc was developed by the Philip Low lab at Purdue University.

Juno Therapeutics American biopharmaceutical company

Juno Therapeutics Inc is an American biopharmaceutical company founded in 2013 through a collaboration of the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center and pediatrics partner Seattle Children's Research Institute. The company was launched with an initial investment of $120 million, with a remit to develop a pipeline of cancer immunotherapy drugs. The company raised $300 million through private funding and a further $265 million through their IPO.

Peptide receptor radionuclide therapy Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Gallium 68 PSMA-11 Drug approved by USFDA

Gallium 68 PSMA-11, or Ga 68 PSMA-11, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men. This is the first drug approved by USFDA as a PET imaging agent.

Lutetium (177Lu) vipivotide tetraxetan

Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.

References

  1. 1 2 3 4 5 6 7 Potera, Carol (April 2013). "Exploiting Folate Pathways to Treat Cancer: Endocyte Uses an Imaging Agent to Select Patients Likely to Respond to Its Therapies". Genetic Engineering & Biotechnology News. 33 (7): 12, 14. doi:10.1089/gen.33.7.03.
  2. ↑ "Clinical Trials Update", Genetic Engineering & Biotechnology News , 29 (8): 58, 2009
  3. ↑ Rapaport, Lisa; Spears, Lee (4 February 2011). "Drugmaker Endocyte Rises 29% After Initial Public Offering". Bloomberg.
  4. ↑ Taylor, Nick Paul (2018-10-18). "Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push". Fierce Biotech. Retrieved 2022-04-13.
  5. ↑ "Endocyte's kidney conjugates get right to the spot - FiercePharma". www.fiercedrugdelivery.com.
  6. 1 2 "Endocyte soars on cancer drug deal with Merck". Reuters. 16 April 2012.
  7. ↑ Leamon, C. P.; Low, P. S. (1 July 1991). "Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis". Proceedings of the National Academy of Sciences. 88 (13): 5572–5576. Bibcode:1991PNAS...88.5572L. doi: 10.1073/pnas.88.13.5572 . PMC   51919 . PMID   2062838.
  8. ↑ Covello, Kelly; Flefleh, Christine; Menard, Krista; Wiebesiek, Amy; McGlinchey, Kelly; Wen, MeiLi; Westhouse, Richard; Reddy, Joe; Vlahov, Iontcho; Hunt, John; Rose, William; Leamon, Chris; Vite, Greg; Lee, Francis (1 May 2008). "Preclinical pharmacology of epothilone-folate conjugate BMS-753493, a tumor-targeting agent selected for clinical development". Cancer Research. 68 (9 Supplement): 2326.
  9. ↑ "Novartis to buy cancer drugmaker Endocyte for $2.1 billion in cash". Reuters. 18 October 2018.
  10. ↑ Miller, John (18 October 2018). "Novartis pushes deeper into nuclear medicine with $2.1 billion deal". Reuters.
  11. ↑ "Novartis announces planned acquisition of Endocyte to expand expertise in radiopharmaceuticals and build on commitment to transformational therapeutic platforms". Novartis.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.