On October 13, 2015 Incyte Corporation (Nasdaq: INCY) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported the expansion of the companies’ ongoing clinical collaboration to include a Phase 3 study evaluating the combination of epacadostat, Incyte’s investigational selective IDO1 inhibitor, with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, as first-line treatment for patients with advanced or metastatic melanoma (Press release, Incyte, OCT 13, 2015, View Source;p=RssLanding&cat=news&id=2096400 [SID:1234507707]). The Phase 3 study, which is expected to begin in the first half of 2016, will be co-funded by Incyte and Merck.

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"We are very pleased to expand our collaboration with Merck and to move the clinical development program for epacadostat in combination with Keytruda into Phase 3," said Hervé Hoppenot, President and Chief Executive Officer of Incyte. "We believe the combination of these two immunotherapies shows promise and, if successfully developed, may help to improve clinical outcomes for patients with metastatic melanoma."

"The initiation of this large Phase 3 study with Incyte in the first-line advanced melanoma treatment setting is an important addition to our robust immunotherapy clinical development program for Keytruda," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "We continue to explore the benefit that Keytruda brings to patients suffering from advanced melanoma when used alone, and we are pleased to be able to add this important combination study with epacadostat to our Keytruda development program."

Under the terms of the agreement Incyte and Merck have also agreed, for a period of two years, not to initiate new pivotal studies of an IDO1 inhibitor in combination with a PD-1/PD-L1 antagonist as first-line therapy in advanced or metastatic melanoma with any third party. During this time, the companies will each offer the other the opportunity to collaborate on any new pivotal study involving an IDO1 inhibitor in combination with a PD-1/PD-L1 antagonist for types of melanoma and lines of therapy outside of the current collaboration agreement.

The agreement is between Incyte and certain subsidiaries and Merck through its subsidiaries.

Epacadostat and Keytruda are part of a class of cancer treatments known as immunotherapies that are designed to enhance the body’s own defenses in fighting cancer; the two therapies target distinct regulatory components of the immune system. IDO1 is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Preclinical evidence suggests that the combination of these two agents may lead to an enhanced anti-tumor immune response compared with either agent alone.

Safety and efficacy data from the ongoing Phase 1/2 study evaluating the combination of epacadostat with Keytruda in patients with advanced malignancies is scheduled to be highlighted as a late-breaking oral presentation (Abstract #142) at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 30th Anniversary Annual Meeting & Associated Programs, November 4–8, 2015 at the Gaylord National Resort & Convention Center in National Harbor, MD.

Metastatic Melanoma

Melanoma, the most serious form of skin cancer, strikes adults of all ages and accounts for approximately five percent of all new cases of cancer in the United States each year. The number of new cases of melanoma continues to rise by almost three percent each year which translates to 76,000 new cases yearly in the U.S. alone.1 The 5-year survival rate for late-stage or metastatic disease is 15 percent.2

About Epacadostat (INCB024360)

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer histologies.

About Keytruda (pembrolizumab) Injection 100mg In Melanoma

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for Keytruda in Melanoma Trials

Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving Keytruda. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold Keytruda for Grade 2; permanently discontinue Keytruda for Grade 3 or 4 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving Keytruda. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold Keytruda for Grade 2 or 3; permanently discontinue Keytruda for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving Keytruda. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue Keytruda.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving Keytruda. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold Keytruda for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue Keytruda for Grade 4 hypophysitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving Keytruda. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving Keytruda. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold Keytruda for Grade 3; permanently discontinue Keytruda for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving Keytruda. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold Keytruda in cases of severe hyperglycemia until metabolic control is achieved.

Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold Keytruda for Grade 2; permanently discontinue Keytruda for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. The following clinically significant immune-mediated adverse reactions occurred in patients treated with Keytruda: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis.

For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold Keytruda and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart Keytruda if the adverse reaction remains at Grade 1 or less. Permanently discontinue Keytruda for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving Keytruda. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue Keytruda.

Based on its mechanism of action, Keytruda may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of Keytruda.

Keytruda was discontinued for adverse reactions in 9% of 411 patients. Adverse reactions, reported in at least two patients, that led to discontinuation of Keytruda were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients. The most frequent serious adverse reactions, reported in 2% or more of patients, were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

No formal pharmacokinetic drug interaction studies have been conducted with Keytruda.

It is not known whether Keytruda is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with Keytruda.

The recommended dose of Keytruda (pembrolizumab) is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with Keytruda. It is not known whether Keytruda is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with Keytruda. Safety and effectiveness of Keytruda have not been established in pediatric patients.

On October 13, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that three abstracts featuring Advaxis’s Lm Technology cancer immunotherapies have been selected for poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 30th Anniversary Annual Meeting & Associated Programs, November 6-8, 2015, at Gaylord National Hotel & Convention Center in National Harbor, Md (Press release, Advaxis, OCT 13, 2015, View Source [SID:1234507706]).

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The poster presentations featuring Advaxis immunotherapies at SITC (Free SITC Whitepaper) 2015 include:

Cohen et al., Phase I/II study of ADXS11-001 or MEDI4736 immunotherapies alone and in combination, in patients with recurrent/metastatic cervical or human papillomavirus (HPV)-positive head and neck cancer.

Haas et al., Phase 1-2 study of ADXS31-142 alone and in combination with pembrolizumab in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC): The KEYNOTE-046 trial.

Ghamande et al., High-dose treatment with ADXS11-001, a Listeria monocytogenes (Lm)-listeriolysin O (LLO) immunotherapy, in women with cervical cancer.

The first poster will feature an ongoing Phase 1/2 clinical trial of Advaxis’s lead immunotherapy candidate axalimogene filolisbac (ADXS-HPV) in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), for the treatment of patients with advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck cancer.

The second poster will feature an ongoing Phase 1/2 clinical trial (KEYNOTE-046) evaluating the combination of ADXS-PSA and Merck’s PD-1 checkpoint inhibitor KEYTRUDA (pembrolizumab) in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC). The KEYNOTE-046 trial is the first-in-human study of ADXS-PSA and the second study initiated to evaluate the use of KEYTRUDA in advanced prostate cancer.

Data from preclinical studies suggest that Advaxis’s Lm Technology immunotherapies in combination with a checkpoint inhibitor, such as durvalumab or KEYTRUDA, may lead to an enhanced anti-tumor immune response. Results from these two studies will determine the future clinical development program for both combinations.

The third poster will include preliminary data from an ongoing Phase 1/2 clinical trial of axalimogene filolisbac at a high dose in patients with recurrent or refractory cervical cancer. Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’s lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.

About ADXS-PSA

ADXS-PSA is an Lm Technology immunotherapy under investigation for targeting the prostate-specific antigen (PSA) associated with prostate cancer. ADXS-PSA is in clinical development both as a monotherapy and in combination with immune checkpoint inhibitors for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

On October 13, 2015 Adaptimmune Therapeutics plc (Nasdaq: ADAP), ("Adaptimmune" or the "Company"), a clinical stage biopharmaceutical company focused on the use of T-cell therapy to treat cancer, reported financial results for the full fiscal year 2015, which ended June 30, 2015 (Press release, Adaptimmune, OCT 13, 2015, View Source [SID:1234507704]).

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"This has been a period of exciting progress throughout our organization, marked by execution on key elements of our growth strategy," commented James Noble, Adaptimmune’s Chief Executive Officer. "We successfully completed our initial public offering in May, and continued to scale up the organization in the U.S. and U.K. to execute on our clinical development and research priorities. From a clinical perspective, we generated strong momentum in our pipeline of affinity enhanced T-cell therapies and have seen encouraging response rates to our NY-ESO-1 affinity enhanced T-cell therapy, which we are developing with GSK, in Phase I/II trials in patients with solid and hematologic cancers. We have also demonstrated durable persistence and long-term expression of the TCR on the cell surface. Our clinical momentum has also included the approval of our Investigational New Drug (IND) application for our affinity enhanced T-cell therapy targeting MAGE-A10, as well as the start of dosing in our expanded study of our NY-ESO-1 affinity enhanced T-cell therapy in patients with synovial sarcoma. Finally, we have a rapidly growing number of active
research programs which puts us in a strong position to deliver our ambitious goal of new INDs each year from 2016 onwards."

Mr. Noble continued, "From a corporate perspective, we have nearly doubled our team since our IPO, having recruited exceptional clinical and manufacturing professionals and expanded our highly skilled research and development team. To accommodate this essential expansion and further growth, we recently announced the commencement of construction for state-of-the-art manufacturing and research facilities in the U.S. and U.K., respectively. This has literally laid a firm foundation for Adaptimmune going forward, enabling us to enter 2016 well placed to deliver key data from our ongoing studies, build clinical experience with our affinity enhanced T-cell therapies, and explore ways to further enhance the rate, depth and durability of responses to them."

Corporate and Clinical Highlights:

• Successfully completed IPO and listed on NASDAQ Global Select Market, raising $176 million in net proceeds; current cash is expected to support global operations for approximately three years;
• Initiated dosing in expanded Phase I/II trial of affinity enhanced T-cell therapy targeting NY-ESO-1 in synovial sarcoma patients.Based on encouraging results seen in the first 12 synovial sarcoma patients, the trial has been expanded to include an additional 20 patients in two cohorts, triggering further milestone payments from GSK;
• Secured publication of data detailing the persistence, tumor trafficking, antitumor effect and safety profile of Adaptimmune’s affinity enhanced T-cell therapy in patients with advanced multiple myeloma in Nature Medicine;
• Presented data from ongoing clinical studies with our NY-ESO-1 T-cell therapy across a number of cancer targets at multiple medical conferences, including the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2015 annual meeting, 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, and the 18th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) (ASCGT);
• Investigational New Drug (IND) application for Phase I/II studies of our MAGE A-10 T-cell therapy filed and now open in the U.S.; dosing in non-small cell lung cancer study anticipated to start in 2015;
• Increased number of research programs for new therapeutic targets from nine to 12; validation of additional targets ongoing toward goal of filing new INDs each year from 2016 onwards.
• Continued execution of growth strategy to build out clinical capabilities to support development of clinical and preclinical pipeline; Company grew from 39 full-time equivalent employees as of July 1, 2014 to 190 as of October 9, 2015; and
• Signed lease agreements in Philadelphia, PA for new fully integrated office, laboratory and cGMP CMC / manufacturing facility, and in Oxfordshire, U.K. for new research and development facility.

Full Fiscal Year 2015 Financial Results

• Cash position: As of June 30, 2015, Adaptimmune had $284 million (£181 million) in cash, cash equivalents, and asset investments, compared to $46.9 million (£30.1 million) as of June 30, 2014.

• Cash Burn: Operating cash outflows were $32.7 million (£20.8 million) related to the growth of Adaptimmune’s business, including $23.2 million (£14.7 million) of R&D expenditure. The overall net increase in cash and cash equivalents of $181.7 million (£115.6 million) and current asset investments of $55.3 million (£35.2 million) in the 12 months ended June 30, 2015 was primarily due to net proceeds on the Series A round and IPO of $275.2 million (£174.7 million).

• Revenue: For the fiscal year ended June 30, 2015, revenue was $10.7 million (£6.8 million) compared to $0.6 million (£0.3 million) for full fiscal year 2014. The increase in 2015 was primarily due to a full year of recognition of revenue under the collaboration and license agreement with GSK, which was announced in June 2014.

• Research and development (R&D) expense: Research and development expenses were $23.2 million (£14.7 million) for fiscal year 2015 compared to $11.6 million (£7.4 million) in fiscal year 2014, primarily due to increased costs associated with ongoing NY-ESO-1 TCR clinical trials, evaluation and validation of additional targets, preparing for NSCLC studies with the Company’s NY-ESO-1 and MAGE A-10 T-cell therapies, personnel expenses including non-cash stock-based compensation, production costs, costs associated with obtaining patents and other intellectual property, and costs related to the Company’s growing operations.

• General and administrative (G&A) expense: General and administrative expenses were $11.3 million (£7.2 million) for fiscal year 2015 compared to $2.5 million (£1.6 million) in fiscal year 2014, primarily due to increased personnel expenses, including non-cash stock-based compensation, and other expenses to support the Company’s growing operations, and the requirements of being a public company.

• Net loss: net loss attributable to common stockholders was $21.6 million (£13.7 million), or $(0.07) per ordinary share (or £(0.04) per ordinary share) for fiscal year 2015.

Fiscal Year Transition
Adaptimmune is transitioning from a June 30 fiscal year end to a December 31 fiscal year end to align more closely with sector comparators, and will be changing its accounting standard from International Financial Reporting Standards (IFRS) to U.S. Generally Accepted Accounting Principles (GAAP) starting in January 2016. The Company will file a form 20-F containing audited financial statements prepared under IFRS covering the period from July 1, 2015 to December 31, 2015 followed by a form 10-K containing audited financial statements prepared under U.S. GAAPcovering the calendar year 2016. As a result, the Company is providing cash burn guidance for the 18 month period between July 1, 2015 and December 31, 2016.

Financial Guidance
For the six months from July 1, 2015 to December 31, 2015, the Company expects its cash burn to be between $20 and $30 million, excluding cash burn associated with business development activities. For the full year 2016, the Company expects its cash burn to be between $80 and $100 million, excluding cash burn associated with business development activities, and expects its cash position at December 31, 2016, including cash, cash equivalents, and asset investments, to be at least $150 million.

On October 13, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported that the U.S. Patent and Trademark Office (USPTO) has issued the first two U.S. patents protecting tarloxotinib bromide*, or "tarloxotinib," the Company’s proprietary hypoxia-activated, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor exclusively licensed from the University of Auckland, New Zealand (Press release, Threshold Pharmaceuticals, OCT 13, 2015, View Source [SID:1234507703]). The first patent, U.S. Patent No. 9,073,916, generically covers a structural class of EGFR tyrosine kinase inhibitor prodrugs, including tarloxotinib, and pharmaceutical compositions containing this structural class of prodrugs. The second patent, U.S. Patent No. 9,101,632, specifically covers the compound tarloxotinib and pharmaceutical compositions containing it.

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"These two patents provide fundamental intellectual property protection for tarloxotinib, which is the subject of two ongoing Phase 2 clinical trials for the treatment of patients with mutant EGFR-positive non-small cell lung cancer and patients with squamous cell cancers of the head and neck or skin," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "Currently, treatment with EGFR inhibitors has limited efficacy because side effects can prevent effective doses from being achieved. We believe that more effective dosing may be achievable with tarloxotinib, which is designed to release an irreversible EGFR tyrosine kinase inhibitor selectively under hypoxic conditions commonly found within solid tumors. Tumor-selective activation of tarloxotinib may allow for greater inhibition of EGFR signaling within the tumor while limiting systemic side effects, potentially leading to better outcomes for patients with EGFR-dependent cancers."

*Tarloxotinib bromide is the proposed International Nonproprietary Name.

About Non-Small Cell Lung Cancer
Lung cancer is the most common cause of death from cancer worldwide; an estimated 1.8 million new cases were diagnosed in 2012.1 The most common type of lung cancer, non-small cell lung cancer (NSCLC), accounts for approximately 85 to 90 percent of cases.2 EGFR activating mutations occur in approximately 10 percent of NSCLC cases in Caucasian patients and up to 35 percent in Asian patients.3 Tarceva, Iressa, and Gilotrif are the first- and second-generation EGFR inhibitors currently approved for patients with the EGFR activating mutations. Nearly all patients ultimately progress on these therapies due to a variety of resistance mechanisms.

One largely unexplored mechanism of treatment resistance is through expression of not only mutant EGFR but also through the emergence of normal, or "wild-type" EGFR, and its subsequent stimulation by growth factors produced in the tumor microenvironment. Hypoxia upregulates the wild-type EGFR protein and its ligand TGF-alpha, leading to elevated EGFR signaling.4,5 Tumors that are heterozygous for EGFR (containing both wild-type EGFR and mutant EGFR) are associated with worse outcomes than is the case with homozygous mutant EGFR.6 Heterozygous disease has also been proposed as a cause of resistance to EGFR inhibitors.7 Tarloxotinib, which is designed to inhibit both mutant as well as wild-type EGFR in a tumor-selective manner, may effectively address these potentially important mechanisms of treatment resistance.

About Squamous Cell Carcinomas Head and Neck
Most head and neck cancers, which include cancers of the larynx (voice box), throat, lips, mouth, nose, and salivary glands, begin in the squamous cells that line the moist surfaces inside the head and neck, and are therefore referred to as squamous cell carcinomas of the head and neck (SCCHN). SCCHN is diagnosed in approximately 59,000 people in the U.S. annually and is responsible for some 12,000 deaths.8 In the recurrent/metastatic setting, chemotherapy or cetuximab monotherapy is the standard of care with response rates are about ten percent and disease progression occurs within two to three months.9

About Squamous Cell Carcinomas of the Skin
Non-melanoma skin cancers typically resulting from chronic sun exposure or other sources of ultraviolet rays are the most common types of cancer. Twenty percent of these skin cancers originate from squamous cells normally present in the outer layers of the skin (SCCS); five percent of SCCS will become locally advanced, recur, or metastasize. In the U.S., approximately 2,000 deaths per year are attributed to SCCS.10 As with SCCHN, SCCS is associated with EGFR overexpression and appear to be responsive to EGFR inhibitor therapy.11

About Tarloxotinib Bromide
Tarloxotinib bromide, or "tarloxotinib," is a prodrug designed to selectively release a covalent (irreversible) EGFR tyrosine kinase inhibitor under severe hypoxia, a feature of many solid tumors. Accordingly, tarloxotinib has the potential to effectively shut down aberrant EGFR signaling in a tumor-selective manner, thus potentially avoiding or reducing the systemic side effects associated with currently available EGFR tyrosine kinase inhibitors. Tarloxotinib is currently being evaluated in two Phase 2 proof-of-concept trials: one for the treatment of patients with mutant EGFR-positive, T790M-negative advanced non-small cell lung cancer progressing on an EGFR tyrosine kinase inhibitor, and the other for patients with recurrent or metastatic squamous cell carcinomas of the head and neck or skin. Threshold licensed exclusive worldwide rights to tarloxotinib from the University of Auckland, New Zealand, in September 2014.