Genentech

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Genentech Inc.

Genentech Headquarters located at South San Francisco, CA

Genentech Inc. is a biotechnology corporation headquartered in South San Francisco, California. Since 2009, Genentech has been a subsidiary of the Roche Group, a Swiss healthcare company. [1] Genentech boasts a staggering $17.3 billion revenue worldwide [2] and employs nearly 13,300 people across the globe. The corporation holds approximately 11,300 patents and has 38 medicines currently out in the market with an additional 46 molecules in clinical trials or currently in their pipeline. Ian Clark is the chief executive officer of Genentech and was appointed to his role in January of 2010. The biotech giant has 785,000 square feet solely devoted to research at its headquarters in San Francisco and at their additional manufacturing facilities in Vacaville, California, Oceanside, California, and Hillsboro, Oregon. [3] These manufacturing plants also have the capacity to produce approximately 330,000 liters of products at a time, based on the size of their bioreactors.[4]

The branches of research that Genentech currently studies includes oncology, immunology, tissue growth and repair, ophthalmology, metabolism, neuroscience, and infectious diseases. Genentech’s portfolio includes major success Oncology medicines such as Rituxan, Avasin, and Herceptin. [3][4]

History

Boyer(left) and Swanson(right) pictured together in 1976 [2]

Genentech was co-founded on April 7th, 1976 by biochemist Herbert Boyer and venture capitalist Robert Swanson. Boyer, at the time, was considered to be one of the pioneers in biotechnology and he demonstrated this with his breakthrough work with restriction enzymes in 1973 [2]. Boyer and his Stanford colleague, Stanley Cohen showed that restriction enzymes could be used to cut DNA fragments and then inserted into a similar plasmid vector via ligation. This process became its own scientific field called recombinant DNA technology, thus giving Boyer a household name. Robert Swanson became intrigued by Boyer and requested a meeting with him. The two hit it off with Swanson truly believing that Boyer's recombinant DNA technology could be a major commercial selling platform and with that the biotechnology giant, Genentech was born. In 1977, Genentech had its first real breakthrough as a company. The company's scientists and researchers had successfully produced Somatostatin, the first human protein, by inserting the gene into an E.coli plasmid. A year later, Genentech was able to clone synthetic human insulin, which gave the company its second massive innovation. Genentech, then took over Wall Street when it went public in 1980, by raising $35 million with an offering, in which leapt its $35 a share to a high of $88 a share within hours, which is one the stock markets largest rise ups, still to date [5].

Other historical timelines [5]

Herb Heynecker at Genentech’s first bio-fermentor in 1978 [2]

1982: Synthetic Human Insulin (Humulin) was marketed with the help of Eli Lilly and Company

1985: Received approval from FDA to market first product, Protropin. Protropin is a growth hormone for children with growth deficiency. This was the first recombinant pharmaceutical product to be manufactured and marketed by a biotechnology company.

1987: Genentech's second product, Activase gained FDA approval.

1990: Roche Holding Ltl from Switzerland, takes a majority holding of Genentech Inc.

1992: The Founders Research Center was opened, in honor of Boyer and Swanson, aimed to recognize their visions in biotechnology.

1993: Received FDA approval for the drugs Pulmozyme and Nutropin.

1995: Roche takes over Genentech's European and Canadian sales

1997: Partnered with IDEC Pharmaceuticals (now Biogen Idec Inc.), received FDA approval to market Rituxan.

1998: Humanized antibody Herceptin received FDA approval, opens new $250 million manufacturing facility

1999: Settled a patent dispute relating Protropin, human growth hormone, with University of California for $200 million.

2000: Received FDA approval for TNKase.

2003: Received FDA approval for the drugs Xolair and Raptiva.

2004: Received approval to market Avastin. Avastin is the first FDA approved therapy to tackle angiogenesis.

2005: Purchased Biogen Idec’s biologics manufacturing facility in Oceanside, California.

2007: Finalized acquisition of Tanox, a pharmaceutical company based in Houston, Texas, which allowed Genentech to improve the business of Xolair.

2009: Roche acquires all of Genentech's stock shares.

2010: Received FDA approval for Tarceva as a maintenance treatment for patients with locally advanced or metastatic non-small lung cancer (NSCLC).

2012: Erivedge was approved for the treatment of adults with a type of skin cancer, called basal cell carcinoma (BCC), Tamiflu was FDA approved.

2013: Gazyva and Kadcyla are approved.

2015: Alecensa and Cotellic are FDA approved.

2016: Venclexta and Tecentriq are FDA approved.

List of All Products

Genentech currently has 38 different medicines that are on the market with FDA approval. The products name and its chemical name are as follows:

Actemra (tocilizumab)
Activase (alteplase)
Alecensa (alectinib)
Avastin (bevacizumab)
Boniva Injection (ibandronate sodium)
Boniva Tablets (ibandronate sodium)
Cathflo Activase (alteplase)
CellCept (mycophenolate mofetil)
Copegus (ribavirin)
Cotellic (cobimetinib)
Cytovene (ganciclovir)
Erivedge (vismodegib)
Esbriet (pirfenidone)
Fuzeon (enfuvirtide)
Gazyva (obinutuzumab)
Herceptin (trastuzumab)
Invirase (saquinavir mesylate)
Kadcyla (ado-trastuzumab emtansine)
Klonopin (clonazepam)
Lucentis (ranibizumab injection)
Nutropin AQ (somatropin for injection)
Ocrevus (ocrelizumab)
Pegasys (peginterferon alfa-2a)
Perjeta (pertuzumab)
Pulmozyme (dornase alfa)
Rituxan (rituximab (oncology))
Rituxan (rituximab (immunology))
Tamiflu (oseltamivir phosphate)
Tarceva (erlotinib)
Tecentriq (atezolizumab)
TNKase (tenecteplase)
Valcyte (valganciclovir hydrochloride)
Valium (diazepam)
Venclexta (venetoclax)
Xeloda (capecitabine)
Xenical (orlistat)
Xolair (omalizumab)
Zelboraf (vemurafenib)

Genentech's Major Products

Rituxan

Rituximab targets B cells by binding to protein CD20 [6]

Rituxan, also known as its generic name Rituximab, is a chimeric monoclonal antibody that can be used alone or with chemotherapy. It targets and attaches to the CD20 protein. CD20 are primarily found on the surface of immune system B cells. Rituxan disrupts B cells by aiding the immune system destroy cancer cells and destroying the cancer cell on its own. It downregulates B cell receptor and induces apoptosis of CD20+ cells [6][7]. These combined effect results in the removal of B cells, allowing healthy B cells to develop from lymphoid stem cells.

Rituxan is used to treat Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia. These diseases are characterized by excessive number of B cells, overactive B cells, or dysfunctional B cells. Genentech classified Rituxan as a specialty drug. Rituxan is the best-selling cancer drug according to industry data accumulating over $7 billion in sales [3].

Avastin

Avastin is effective in inhibiting angiogenesis when binds directly to VEGF [8]

Avastin, also known as Bevacizumab, is a recombinant humanized monoclonal antibody that is used as an angiogenesis inhibitor essentially slows the growth of new blood vessels. Avastin blocks angiogenesis by directly binding to endothelial growth factor (VEGF) [4]. VEGF is a chemical signal that stimulates angiogenesis and some cancer cells make too much VEGF [8]. Avastin is used to block the blood supply that feeds the tumor and thus preventing the tumor from growing [9]. It is demonstrated in preclinical models that sustained VEGF inhibition may be key to maintain tumor regression.

Avastin was approved to treat lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain. Adverse effects include hypertension and heightened risk of bleeding. Avastin was first approved in 2004 and amassed over $6 billion in sales [3].

Herceptin

Herceptin inhibits endurance and propagation of tumors by binding to HER2 [11]

Herceptin, also known as Trastuzumab, is a humanized monoclonal antibody that inhibits Human Epidermal growth factor Receptor 2-positive or HER2/neu receptor. Overexpression of HER2 gene has been shown to play a principal role in the development of certain aggressive types of breast cancer. The HER2 gene makes a protein known as HER2 receptors [10]. These HER2 receptors are embedded in the cell membrane and helps receive signals that stimulate the cell to grow and multiply. In most breast cancer patients, HER2 is over-expressed and causes cancer cells to multiply uncontrollably. Herceptin attaches itself to the HER2 receptors on the surface of breast cancer cells. This blocks HER2 from receiving growth signals [11].

Genentech partnered with UCLA to develop Herceptin and gained approval in 1998. Herceptin is known to reduce risk of cancer returning after surgery when used in early stage. Adverse effects include heart failure and left ventricular ejection fraction decline. Herceptin sales grossed over $6 billion since its inception [3].

Recent Innovations and Research

Tecentriq (atezolizumab)

In 2016, Genentech's product of Tecentriq (atezolizumab) was approved by the FDA to treat for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer. Tecentriq, is a a programmed death ligand that targets the death of the protein of PD-L1 found in cancer cells. The protein PDL1 is found on cancer cells and can make the cancer cells hide themselves from the immune system antibodies. Thus, when Tecentriq enters the system, it kills the PDL1 protein by blocking it and gives the body's immune system (creation of T cells) a better chance to eliminate the cancer cells. Tecentriq is administered to a patient via intravenous infusion for 60 minutes every three weeks with 1200 mg given in each dose. The drug is specific to only certain restrictions when either having urothelial carcinoma or non-small lung cancer. For urothelial carcinoma, a form of bladder cancer, Tecentriq can only be used when the cancer has spread and cannot be removed by surgery, and the patient has tried chemotherapy containing platinum, which was unsuccessful. As for non-small cell lung cancer, Tecentriq is used when after platinum chemotherapy is completed and the cancer is still, as studies have shown that the Tecentriq is much more successful than a second round of chemotherapy.

On April 17, 2017, Tecentriq gained accelerated approval by the FDA to be used for patients with metastatic urothelial carcinoma who could not use cisplatin chemotherapy as a treatment option. More than half of people who are diagnosed with advanced urothelial carcinoma are unable to use cisplatin as a chemotherapy to help cure the cancer. With this early approval by the FDA, from a Stage II trial that was quite successful, many patients now have an option to treat the urothelial carcinoma. Even though Tecentriq received approval from Stage II by having more than 50% of the patients in the study respond to the drug, Genentech is currently still conducting a Stage III trial to confirm the results that the drug is effective for patients that can not use cisplatin chemotherapy.

There are many side effects to Tecentriq. The biggest and most important side effect to Tecentriq is the fact that it can possibly effect the organs in the patients body that have nothing wrong with them. Tecentriq can create pneumonitis in the lungs, hepatitis in the liver, colitis in the intestines, stop function in the hormone glands, neuropathy or meningitis in the nervous system, or cause serious eye inflammation. The most common side effects, however are slightly different when treating for metastatic urothelial carcinoma or non-small cell lung cancer. In urothelial carcinoma, the most common side effects are fatigue, lost of appetite, fever, urinary tract infection, constipation, and nausea. In non-small cell lung cancer, the side effects are fatigue, lost of appetite, nausea, cough, shortness of breath, and constipation.

Lucentis (ranibizumab injection) for Diabetic Retinopathy

Lucentis was first approved by the FDA in 2006 to treat patients suffering from wet age-related macular degeneration (wet AMD) and in 2012 to treat for diabetic macular edema (DME), both of which cause blindness to the eye. On April 17, 2017, Lucentis was proven with FDA approval to be able to treat for all forms of diabetic retinopathy, which directly damages the retina. Diabetic retinopathy is when poorly controlled blood sugar counts stemming from diabetes, causes the blood vessels in tissue behind the eyes (retina) to leak, thus effecting a person's vision with the excess fluid. The leaking of the blood vessels in the retina is caused by the overexpression of the VEGF protein (vascular endothelial growth factor), which is essential in vessels. Diabetic retinopathy is the leading cause of vision loss in working class U.S. adults between 20-74 and effects 7.7 million Americans, thus making a solution a necessity. Lucentis is therefore designed to inhibit VEGF-A by binding to it and eliminating its angiogenesis and hyperpermeability, which has shown in a most recent study to greatly relieve diabetic retinopathy.

The process of receiving Lucentis to the body is done through a direct injection to the infected eye. The process was done every month with 0.3 mg of Lucentis injected each time. There are some minor and some serious side effects to Lucentis. The minor side effects include eye pain, increased eye pressure, redness of the eye, and small specks in a person's vision. The major side effects of Lucentis are cataracts, detached retinas, and serious infections inside the eye.

Career Opportunities [12]

There are currently 318 job openings posted on the Genentech website (https://www.gene.com/careers/find-a-job) as of April 23rd, 2017. The majority of available positions look for chemistry, biochemistry, mechanical engineering, and chemical engineering majors although there are also jobs in marketing and business analysis. Experience level varies by the job description, but Genentech offers jobs to student internships, regular employees, special programs and temporary workers at all of their business and manufacturing sites. Entry level bachelors are encouraged to apply to the rotation programs. Process development rotation program associates will experience four six month assignments over the course of two years in different areas within US Biologics Technical Development. Genentech hires approximately 3500 people a year in a four step process listed as Discovery, Evaluation, Offer, and Welcome.

Awards & Recognition [13]

Founders of Genentech [2]

“100 Best Companies to Work For” awarded for the 18th consecutive year – Fortune (2016)

“Best Places to Work for LGBT Equality”- Corporate Equality Index (2016)

“100 Best Companies for Working Mothers” – Working Mother Magazine (2015)

“Healthiest Companies to Work For in America” – Greatist.com (2014)

“The World’s 50 Most Innovative Companies” – Fast Company (2012)

References

[1] Smith Hughes, S. (2011). Genentech: The Beginnings of Biotech. [1]
[2] Godar, M. (2015). History of Biotech: How Modern Biotechnology Started-Up 39 Years Ago. [2]
[3] Mulcahy, N. (2014).Top 10 Best-Selling Cancer Drugs Globally. Medscape. [3]
[4] Genentech Inc. (2017). Our Medicines. Genentech Inc. [4]
[5] Genentech Inc. (2017). A History of Firsts. Genentech Inc. [5]
[6] Weiner GJ. (2010). Rituximab: mechanism of action. Seminars in hematology.115-123. [6]
[7] Genentech Inc & Biogen Inc. (2017). Chronic Lymphocytic Leukemia. RITUXAN®. [7]
[8] Genentech Inc. (2017). Avastin® (Bevacizumab). [8]
[9] Genentech Inc. (2017). About Avastin: Proposed Mechanism Of Action. Avastin® (Bevacizumab). [9]
[10] Genentech Inc. (2017). Fight HER2+ Breast Cancer With Herceptin. Herceptin® (Trastuzumab). [10]
[11] Hudis, C. (2007). Trastuzumab — Mechanism Of Action And Use In Clinical Practice. New England Journal of Medicine (357.1), 39-51. [11]
[12] Genentech Inc. (2017). Job Search. Genentech Inc. [12]
[13] Genentech Inc. (2017). Awards and Recognition. Genentech Inc. [13]