On February 27, 2019 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) reported completion of enrollment into the ongoing phase 2 expansion of the ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) in patients with unresectable or metastatic melanoma following failure of PD-1 inhibitor treatment (Press release, Idera Pharmaceuticals, FEB 27, 2019, View Source [SID1234533745]).

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52 patients have been dosed in the trial which included two separate patient groups. The company completed the targeted enrollment of 40 patients in the primary enrollment population, constituting patients who are naïve to prior ipilimumab treatment in the metastatic setting. This patient population mirrors the enrollment for the ILLUMINATE-301 phase 3 pivotal trial. The secondary exploratory enrollment population targeted up to 20 patients who had prior ipilimumab treatment in the metastatic setting.

The ILLUMINATE-204 trial is a multi-center trial being conducted at 10 sites throughout the United States.

The company is currently enrolling ILLUMINATE-301, a global, multi-center, randomized Phase 3 trial that compares effectiveness and safety between two treatment groups: tilsotolimod combined with ipilimumab versus ipilimumab given alone. This trial is being conducted at up to 100 centers with a target enrollment of 308 patients. Enrollment remains on track and is expected to be completed in the 4th quarter of 2019.

The company also recently received notice from the U.S. Food and Drug Administration that the company can proceed to implement the ILLUMINATE-206 clinical trial under a new Investigational New Drug (IND) Application. The ILLUMINATE-206 trial will test the safety and effectiveness of tilsotolimod in combination with ipilimumab and nivolumab in treating patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) and Microsatellite Stable Colorectal Cancer (MSS-CRC). The ILLUMINATE-206 trial is expected to initiate in the second quarter of 2019.

"We made tremendous progress with the clinical development of tilsotolimod in the second half of 2018, and enrollment in the phase 3 study in patients with melanoma progressing on PD-1 therapy is tracking to complete by the end of 2019." stated Joanna Horobin, M.B. Ch.B, Idera’s Chief Medical Officer. "Oncologists are enthusiastic to extend the use of tilsotolimod to potentially improve the outcome of immuno-therapy for other patient populations, such as head and neck cancer, and in microsatellite stable CRC where so far immunotherapy outcomes have not been optimal."

As a reminder, the company provided an interim data update from the ILLUMINATE-204 trial in December 2018.

Summary of ILLUMINATE-204 Key Findings from the December 2018 Update:

37 patients dosed with 8 mg of tilsotolimod in combination with ipilimumab were evaluated for the December 2018 update;
All 37 patients were evaluable for safety;
The combination regimen continues to be generally well tolerated. 9/37 subjects (24.3%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add immune-related toxicity versus ipilimumab alone;
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours;
34 patients were evaluable for efficacy;
Responses, including 3 Complete Responses (CR), were observed in 11 of the 34 evaluable patients (32.4%);
Duration of response ranges from > 1 month to > 30 months, with 36% of responses ongoing at the time of the report;
Per RECIST v1.1, the Overall Response Rate (ORR) is 29.4%; one patient with an unconfirmed Partial Response (uPR) at the end of treatment assessment progressed due to a new lesion at the 3-month follow-up disease assessment;
Overall, 26 patients out of 34 evaluable for efficacy (76.5%) experienced disease control (CR, PR, or Stable Disease [SD]);
Analysis of spider plots show tumor shrinkage in both injected and uninjected lesions, indicating an abscopal effect;
Responding subjects include one patient with mucosal melanoma and one patient with acral melanoma, two forms of melanoma that are particularly difficult to treat; and
Importantly, 2 of 5 patients with prior ipilimumab experience achieved responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance.
Additionally:

A RECIST v1.1 PR of > 2.5 years is ongoing in 1 patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
A RECIST v1.1 CR of > 1 year is ongoing in 1 patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the tumor-specific T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-301
The ILLUMINATE-301 study (2125-MEL-301) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda (pembrolizumab) or Opdivo (nivolumab) has failed. ILLUMINATE-301 is a global, multi-center, randomized Phase 3 study that compares the effectiveness and safety between two treatment groups: IMO-2125 combined with ipilimumab (Yervoy) versus ipilimumab given alone.

For additional details about ILLUMINATE-301, please go to clinicaltrials.gov and search for study identifier NCT03445533.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About ILLUMINATE-206
The ILLUMINATE-206 study (2125-206) is a Phase 2 multi-center, multi-cohort study of intratumoral tilsotolimod in combination with nivolumab and ipilimumab in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are either immunotherapy naïve and immunotherapy refractory and immunotherapy naïve patients with Microsatellite Stable Colorectal Cancer (MSS-CRC). The trial is expected to open for enrollment in the second quarter of 2019.

About Metastatic Melanoma
Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

On February 27, 2019 Starpharma (ASX: SPL, OTCQX: SPHRY) reported its interim report and financial results for the half-year ended 31 December 2018 (Press release, Starpharma, FEB 27, 2019, View Source [SID1234533744]).

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Financial Summary

Reported loss of $7.3M (Dec 2017: $6.2M); and
Cash position at 31 December 2018 of $44.4M (June 2018: $51.3M), which excludes the expected $4.0M FY18 R&D tax incentive to be received.
VivaGel

VivaGel BV was licensed to ITF Pharma, Inc., for the US for milestones of up to US$101M in addition to escalating, double-digit royalties;
Starpharma and its partners, Mundipharma and Aspen, undertook extensive preparations for the upcoming launches of VivaGel BV in multiple regions scheduled for the first half of 2019. Extensive marketing activities such as packaging design, sales staff training, promotional material development, and launch meetings occurred in parallel with supply chain activities. Manufactured product has been delivered to Aspen subsequent to half-year end, and manufacturing of product for Europe is well-advanced;
US FDA completed its review of the VivaGel BV NDA and advised it requires confirmatory clinical data prior to approval. In preparation for a meeting with the FDA to discuss the data required, Starpharma has been working closely with expert FDA consultants and is currently awaiting confirmation of the meeting date;
VivaGel condom received final regulatory approval in Japan and Starpharma’s partner, Okamoto, commenced launch activities; and
Positive independent market research was conducted in the US for SPL7013 ophthalmic drops for viral conjunctivitis and a patent was granted for the product.
DEP Drug Delivery

Recruitment activities progressed well for two DEP clinical trials – for DEP docetaxel (phase 2) and DEP cabazitaxel (phase 1 / 2), with new sites opened to support recruitment. Efficacy signals have been observed in a number of patients and both products continue to exhibit a notable lack of bone marrow toxicity and other common side effects including hair-loss, anaphylaxis and oedema;
Final preclinical work for the DEP irinotecan phase 1 / 2 trial was completed, study product was manufactured, and other trial preparations, including CRO/site selection, are well advanced ahead of the planned trial commencement later in FY19;
AstraZeneca’s first patent application on DEP Bcl2/xL inhibitor conjugates was published and included compelling efficacy data on DEP Bcl2/xL inhibitor conjugates, both alone and in combination with market-leading anti-cancer treatments, in various human leukemia models;
DEP irinotecan showed impressive efficacy and safety benefits over standard irinotecan in combination with 5-FU in a human pancreatic cancer model;
DEP docetaxel & DEP cabazitaxel outperformed both gemcitabine & Abraxane in a human pancreatic cancer model; and
A range of DEP radiopharmaceutical and other DEP candidates have been made and are currently undergoing testing in a variety of models.
Starpharma concluded the half-year in a strong financial position with a cash balance of $44.4 million, which does not include the $4.0M FY18 R&D tax incentive expected to be received after 31 December 2018. The net loss after tax for the half-year of $7.3 million (Dec 2017: $6.2 million) reflects investment across the VivaGel and DEP portfolio, including DEP docetaxel, DEP cabazitaxel, and DEP irinotecan. Expenditure includes an increased investment in commercialisation, regulatory and operating costs associated with the US VivaGel BV licence and the preparation for product launch in a number of territories.

Starpharma’s CEO, Dr Jackie Fairley, commented: "We achieved several important milestones in the VivaGel portfolio during the half-year, including signing a US licence for VivaGel BV with ITF Pharma, Inc. We were clearly surprised and disappointed by the FDA’s request for confirmatory data and we are working with expert FDA consultants to expedite this process. In non-US territories, launch activities are in the final stages as we approach the launch of VivaGel BV in Australia and Europe (1HCY19). We also continue to work closely with our partner, Mundipharma, on further registrations to support launches in several other regions."

Commenting on the DEP drug delivery portfolio, Dr Fairley said: "We’re pleased to see efficacy signals once again in both our DEP clinical trials as well as a notable lack of bone marrow toxicity and other common side effects. An abundance of positive data from the DEP platform, both preclinical and clinical, continues to build amid partnered program discussions with a number of multinational and US pharmaceutical companies. Our first partnered program with AstraZeneca for AZD0466 is expected to commence clinical trials this year and preparations at AstraZeneca for this activity continue with priority. This partnered program is just one example of the value that can be generated from our unique DEP platform."

Dr Fairley concluded: "We expect to announce a number of key milestones throughout 2019, in addition to the launch of VivaGel BV in Australia and Europe, and regulatory progress across a range of markets, including the US; launch of the VivaGel condom in Japan; regulatory approval of the VivaGel condom in other regions; and progress across internal and partnered DEP programs including commencement of the DEP irinotecan and AZD0466 clinical trials."

On February 27, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported presentations highlighting next-generation CAR T platform and mesothelin-targeted CAR T clinical safety and efficacy results from Memorial Sloan Kettering Cancer Center (MSK) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Atara Biotherapeutics, FEB 27, 2019, View Source [SID1234533742]). The event will be held March 29 to April 3 in Atlanta, Georgia.

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"Atara has established a leading next-generation CAR T portfolio," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Encouraging pre-clinical results at AACR (Free AACR Whitepaper) show the potential of our EBV-specific T cell platform to generate off-the-shelf, allogeneic CAR T immunotherapies. We also look forward to our MSK collaborators’ clinical results of a mesothelin-targeted autologous CAR T for patients with advanced malignant pleural disease."

Mesothelin is a solid tumor-associated antigen that is expressed at high levels on the surface of cells in aggressive solid tumors including mesothelioma, triple-negative breast cancer, ovarian cancer, pancreatic cancer and non-small cell lung cancer. Initial results from an ongoing MSK investigator-sponsored Phase 1 study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with malignant pleural cancers were presented at the 2018 American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting and support activity and safety in patients with advanced mesothelioma1,2. This ongoing Phase 1 dose-escalation study continues to accrue patients and the initial results at ASGCT (Free ASGCT Whitepaper) 2018 showed enhanced response rates when patients were subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor. MSK is also investigating mesothelin-targeted CAR T cells for patients with advanced breast and lung cancer (NCT02792114).

In January 2019, Atara announced an exclusive license and collaboration agreement with MSK to develop a next-generation, mesothelin-targeted CAR T using novel 1XX CAR signaling domain and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies for patients with mesothelin-associated solid tumors.

Abstract 2310: Functional demonstration of CD19 chimeric antigen receptor (CAR) engineered Epstein-Barr virus (EBV) specific T cells: An off-the-shelf, allogeneic CAR T-cell immunotherapy platform
Session Category: Immunology
Session Title: Adoptive Cell Therapy 2
Poster Presentation Date and Time: Monday, April 1, 2019 from 1:00 pm – 5:00 pm EDT
Location: Georgia World Congress Center, Exhibit Hall B
Authors: Blake T. Aftab, Rhine R. Shen, Christina D. Pham, Michelle Wu, Daniel J. Munson
Affiliations: Atara Biotherapeutics
Summary: Atara engineered EBV-specific T cells to express second-generation CD19 CARs, utilizing CD28 or 4-1BB co-stimulatory domains, resulting in high expression of both CD19 CAR and EBV T cell receptor (TCR). The chimeric EBV.CD19.CAR T cells exert potent and specific cytotoxicity against CD19-positive cells but have limited activity against CD19-negative cells. These findings establish feasibility for engineering EBV-specific T cells by leveraging next-generation CAR technologies, and support further development as an off-the-shelf, allogeneic CAR T immunotherapy platform.

Title: A Phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy
Session: Advances in Novel Immunotherapeutics
Clinical Trials Minisymposium Date and Time:Sunday, March 31, 2019 from 3:00 pm – 5:00 pm EDT
Location:Room A411 – Georgia World CC
Authors:Prasad S. Adusumilli, Marjorie Zauderer, Valerie Rusch, Roisin O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Alain Vincent, Elizabeth Halton, Claudia Diamonte, John Pineda, Shanu Modi, Steve Solomon, David R Jones, Renier Brentjens, Isabelle Riviere, Michel Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center

References
1Adusumilli PS, et al. A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CART cells: safety and efficacy – a preliminary report. Abstract 342; 2018 ASGCT (Free ASGCT Whitepaper) Annual Meeting; Chicago, IL; May 16-19, 2018.
2Adusumilli PS, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014 Nov 5;6(261):261ra151. doi: 10.1126/scitranslmed.3010162.

On February 27, 2019 PRA Health Sciences, Inc. ("PRA" or the "Company") (NASDAQ: PRAH) reported financial results for the quarter and year ended December 31, 2018 (Press release, PRA Health Sciences, FEB 27, 2019, View Source;p=irol-newsArticle&ID=2389364 [SID1234533741])

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"We are delighted to have closed out 2018 with another quarter of strong financial results," said Colin Shannon, PRA’s Chief Executive Officer. "Our ability to execute across all of our businesses has allowed us to deliver solid revenue growth and strong bottom-line results. Our key financial metrics continue to improve, as highlighted by our 1.30 net book-to-bill ratio and our expanding margins. We remain focused on providing broad and flexible services to our clients and believe we are well positioned to deliver strong results in 2019."

Net new business for our Clinical Research segment for the three months ended December 31, 2018 was $667.3 million, representing a net book-to-bill ratio of 1.30 for the period. This net new business contributed to an ending backlog of $4.2 billion at December 31, 2018.

For the three months ended December 31, 2018, revenue was $729.6 million, which represents growth of 11.2%, or $73.8 million, compared to the fourth quarter of 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $79.0 million, an increase of 12.0% compared to the fourth quarter of 2017. By segment, the Clinical Research segment generated revenues of $655.6 million, while the Data Solutions segment generated revenues of $74.0 million.

On January 1, 2018, the Company adopted Accounting Standards Codification Topic 606, "Revenue from Contracts with Customers," or ASC 606, using the modified retrospective method for all contracts that were not completed as of January 1, 2018. Prior periods have not been restated under this guidance and remain as previously reported. The primary impact of applying this new guidance on our statement of operations is that (i) we now recognize reimbursements from our customers for payments to investigators as revenue, whereas these payments and costs were previously recorded on a net basis, and (ii) we include all reimbursed costs in the total project costs when measuring our progress under our research contracts instead of recording these amounts on a separate basis.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $20.2 million, which represents growth of 3.6% at actual foreign exchange rates and 4.2% on a constant currency basis.

Direct costs, exclusive of depreciation and amortization, were $365.7 million during the three months ended December 31, 2018 compared to $368.9 million for the three months ended December 31, 2017. The decrease in direct costs was primarily due to a favorable impact of $8.6 million from foreign currency exchange rate fluctuations, which was offset by an increase in salaries and related benefits of $3.6 million in our Clinical Research segment as we continue to ensure appropriate staffing levels and an increase of $1.6 million in our Data Solutions segment. Direct costs were 50.1% of revenue during the fourth quarter of 2018 compared to 56.2% of revenue during the fourth quarter of 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, direct costs were 62.1% of revenue during the fourth quarter of 2018 compared to 64.9% of revenue during the fourth quarter of 2017.

Selling, general and administrative expenses were $96.4 million during the three months ended December 31, 2018 compared to $92.2 million for the three months ended December 31, 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, selling, general and administrative costs were 16.4% of revenue during the fourth quarter of 2018 compared to 16.2% of revenue during the fourth quarter of 2017.

GAAP net income was $71.5 million for the three months ended December 31, 2018, or $1.07 per share on a diluted basis, compared to a GAAP net loss of $16.0 million for the three months ended December 31, 2017, or $0.25 per share on a diluted basis. Our reported net loss for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities.

EBITDA was $124.9 million for the three months ended December 31, 2018, representing an increase of 720.9% compared to the three months ended December 31, 2017. Our EBITDA for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities. Adjusted EBITDA was $136.2 million for the three months ended December 31, 2018, representing growth of 18.8% compared to the three months ended December 31, 2017.

Adjusted net income was $86.9 million for the three months ended December 31, 2018, representing 26.4% growth compared to the three months ended December 31, 2017. Adjusted net income per diluted share was $1.31 for the three months ended December 31, 2018, representing 26.0% growth compared to the three months ended December 31, 2017.

Full Year 2018 Financial Highlights

For the twelve months ended December 31, 2018, revenue was $2,871.9 million, which represents growth of 27.1%, or $612.5 million, compared to the twelve months ended December 31, 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $597.3 million, representing growth of 26.4% compared to the twelve months ended December 31, 2017. By segment, the Clinical Research segment generated revenues of $2,622.4 million, while the Data Solutions segment generated revenues of $249.5 million.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $348.5 million, which represents growth of 17.9% at actual foreign exchange rates and 17.4% on a constant currency basis. Organic revenue growth, excluding the adoption of ASC 606, reimbursement revenue and revenue attributable to our Data Solutions segment, was 10.2% at actual foreign exchange rates and 9.7% on a constant currency basis.

Reported GAAP income from operations was $281.3 million, reported GAAP net income attributable to PRA Health Sciences was $153.9 million and reported GAAP net income attributable to PRA Health Sciences per diluted share was $2.32 for the twelve months ended December 31, 2018.

Adjusted net income was $284.1 million for the twelve months ended December 31, 2018, an improvement of 29.8% compared to the twelve months ended December 31, 2017. Adjusted net income per diluted share was $4.28 for the twelve months ended December 31, 2018, up 28.5% compared to the twelve months ended December 31, 2017.

Full Year 2019 and Q1 2019 Guidance

For full year 2019, the Company expects to achieve total revenues between $3.09 billion and $3.20 billion, representing as reported and constant currency growth of 8% to 11%. On an ASC 605 basis, the Company expects to achieve revenues of between $2.475 billion and $2.57 billion, representing as reported and constant currency growth of 8% to 12%.

We expect GAAP net income per diluted share of between $3.65 and $3.80 per share and adjusted net income per diluted share of between $4.93 and $5.08 per share, representing growth of 15% to 19%. We anticipate an annual effective income tax rate estimate of 24%.

Our effective tax rate may differ from this estimate, due to, among other things, changes to estimates of the geographic allocation of our pre-tax income as well as changes in interpretations, analysis, and additional guidance that may be issued by regulatory agencies as it relates to the Tax Cuts and Jobs Act.

For Q1 2019, the Company expects to achieve total revenues between $720.0 million and $740.0 million, representing as reported growth of 3% to 5% and constant currency growth of 4% to 7%. On an ASC 605 basis, the Company expects to achieve revenues of between $575.0 million and $595.0 million, representing as reported growth of 3% to 6% and constant currency growth of 4% to 7%. The Company expects GAAP net income per diluted share of between $0.74 and $0.79 per share, adjusted net income per diluted share between $1.05 and $1.10 per share, and an annual effective income tax rate of 24%.

Our 2019 guidance assumes a EURO rate of 1.15 and a GBP rate of 1.35 with all other foreign currencies using a rate as of January 31, 2019.

A reconciliation of our non-GAAP measures, including revenue reported on an ASC 605 basis, EBITDA, adjusted EBITDA, adjusted net income, adjusted net income per share and our 2019 guidance, to the corresponding GAAP measures is included in this press release.

Conference Call Details

PRA will host a conference call at 9:00 a.m. ET on February 28, 2019, to discuss the contents of this release and other relevant topics. To participate, please dial (877) 930-8062 within the United States or (253) 336-7647 outside the United States approximately 10 minutes before the scheduled start of the call. The conference ID for the call is 8697447. The conference call will also be accessible, live via audio broadcast, on the Investor Relations section of the PRA website at investors.prahs.com. A replay of the conference call will be available online at investors.prahs.com. In addition, an audio replay of the call will be available for one week following the call and can be accessed by dialing (855) 859-2056 within the United States or (404) 537-3406 outside the United States. The replay ID is 8697447.

Additional Information

A financial supplement with fourth quarter 2018 results, which should be read in conjunction with this press release, may be found in the Investor Relations section of our website at investors.prahs.com in a document titled "Q4 2018 Earnings Presentation."

On February 27, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported its fourth quarter and year-end 2018 financial results and provided a corporate update (Press release, Iovance Biotherapeutics, FEB 27, 2019, View Source [SID1234533740]).

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"Over the past year, we took great strides forward in our goal of advancing TIL therapy towards approval in multiple indications and bringing this one-time treatment to patients who have progressed through existing treatment options," commented Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance Biotherapeutics. "We reported clinical results for our lead program in metastatic melanoma, received acknowledgement from the FDA on a defined path to approval with a single-arm study and have firmly established our optimized, scalable, 22-day manufacturing process. We are well financed to complete the registration-enabling study, Cohort 4, and file the Biologics License Application (BLA) in 2020 for lifileucel. The regenerative medicine advanced therapy (RMAT) designation we received this past year for lifileucel allows for close coordination with the FDA as we move forward. Now that we have demonstrated compelling data in post PD-1 melanoma patients and have received regulatory clarity, we continue our development work in additional indications, such as cervical, while preparing to build internal manufacturing capabilities. Our goals for 2019 will further propel Iovance towards registration and commercialization of TIL therapy."

2018 Highlights

Clinical

·New data from Cohort 2 of lifileucel in the treatment of metastatic melanoma study (C-144-01) was presented in poster and oral presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in November 2018. The presentation described results from 47 consecutively dosed, post PD-1 patients with an objective response rate (ORR) of 38%.1 The most common treatment emergent adverse events observed in this cohort include thrombocytopenia, chills, neutropenia, febrile neutropenia and anaemia.
·In the Phase 2 study of LN-145 for cervical carcinoma (C-145-04) preliminary data was reported in October 2018 for 15 patients yielding an ORR of 27%. Patients in the study had a median of five prior therapies. The safety findings from this study remained consistent with previous reports.

Regulatory

·In May 2018, the company was granted orphan drug designation from the U.S. Food and Drug Administration (FDA) for autologous tumor infiltrating lymphocytes for the treatment of cervical cancer with a tumor size of greater than 2 cm in diameter.
·In September 2018, the company received the Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for lifileucel for the treatment of patients with metastatic melanoma.
·In September 2018, the company held an end of Phase 2 meeting with the FDA during which the agency acknowledged that a single-arm cohort as part of the C-144-01 study can be supportive of initial registration of lifileucel.

Research

·Under a collaboration with Ohio State University, Iovance has developed a product candidate called peripheral blood lymphocytes (PBL). The company anticipates filing an IND for PBL in hematological indications in 2019.

Corporate

·The company completed two underwritten public offerings in 2018 raising approximately $400 million.

2019 Updates

Clinical

·The protocol for the metastatic melanoma study (C-144-01) was amended based on FDA feedback. The trial sites are in process of re-activation for Cohort 4, which is expected to enroll 75 patients. Patient enrollment has commenced.
·The last patient was enrolled in Cohort 2 of the metastatic melanoma study in the fourth quarter of 2018. The company anticipates providing an update on the full cohort of patients at a medical meeting in 2019.
·The protocol for the cervical carcinoma study has been amended to limit the number of prior therapies to no more than three and to exclude patients who have been treated with prior immunotherapy. The company anticipates providing an update on this study at an upcoming medical meeting in 2019.
·The company has dosed over 100 patients with the Gen 2 manufacturing product across multiple studies.

Regulatory

·In February 2019, the company was granted Fast Track designation from the FDA for treatment of patients with recurrent, metastatic, or persistent cervical cancer patients who have progressed while on or after chemotherapy.

Research

·An abstract titled "Persistence of cryopreserved tumor-infiltrating lymphocyte product lifileucel (LN-144) in C-144-01 study of advanced metastatic melanoma" was accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting March 29-April 3, 2019.

Fourth Quarter 2018 Financial Results

Net loss for the fourth quarter 2018 was $32.6 million, or $0.27 per share, compared to net loss of $25.9 million or $0.36 per share for the fourth quarter 2017.

Research and Development expenses were $27.4 million for the fourth quarter 2018, an increase of $6.7 million compared to $20.7 million for the quarter ended December 31, 2017. The increase in Research and Development expenses is attributable to; an increase in Research and Development staff and the related compensation expense, an increase in clinical trial and manufacturing costs due to the initiation of clinical trials in 2018 for new indications and increased number of patients enrolled across all the studies.

General and administrative expenses were $7.5 million for the fourth quarter 2018, an increase of $2.1 million compared to $5.4 million for the fourth quarter ended 2017. The increase in General and Administrative expenses was primarily attributable to an increase in General and Administrative headcount and related compensation expenses and an increase in external professional service fees.

Full Year 2018 Financial Results

Net loss for the year ended December 31, 2018 was $123.6 million, or $1.27 per share, compared to $92.1 million or $1.41 per share for the year ended December 31, 2017.

Research and Development expenses were $99.8 million for the year ended December 31, 2018, an increase of $28.2 million compared to $71.6 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, due to a higher number of full-time employees and dedicated consultants as we expanded our internal research efforts and clinical development programs. Further, clinical trial costs increased due to; higher patient enrollment and an increase in the number of clinical sites for lifileucel and LN-145.

General and Administrative expenses were $28.4 million for the year ended December 31, 2018, an increase of $7.1 million compared to $21.3 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, driven by a higher number of full-time employees and higher stock prices during 2018, and an increase in external professional service fees including preparation and filing of patents.

Cash, Cash Equivalents and Short-term Investments

At December 31, 2018, the company held $468.5 million in cash, cash equivalents and short-term investments, compared to $145.4 million at December 31, 2017. Net cash used in operating activities was $101.2 million during the year ended December 31, 2018.

Iovance anticipates cash, cash equivalents and investments to be between $310 million and $320 million at December 31, 2019.

Webcast and Conference Call

Iovance will host a conference call and live audio webcast to discuss financial results and provide a corporate update today at 4:30 p.m. ET.

To participate in the conference call, please dial 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and reference the access code 7055329. The live webcast can be accessed under "News & Events" in the Investors section of the Company’s website at www.iovance.com, or you may use the link: View Source

A replay of the call will be available from February 27, 2019 at 7:00 p.m. ET to March 6, 2019 at 6:30 p.m. ET. To access the replay, please dial 1-855-859-2056 (domestic) or 1-404-537-3406 (international) and reference the access code 7055329. The archived webcast will be available for thirty days in the Investors section at www.iovance.com.

1 The ORR included one complete response and 17 partial responses, one of which was unconfirmed and pending patient’s subsequent clinical assessment.