On August 10, 2015 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the second quarter 2015 and commented on recent accomplishments and clinical development plans for selinexor, its lead product candidate (Filing, 8-K, Karyopharm, AUG 10, 2015, View Source [SID:1234507152]).

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"Important data describing the clinical benefit of selinexor across multiple solid and hematologic malignancies was presented during the quarter, including single agent anti-tumor activity and durable disease control in patients with recurrent glioblastoma, advanced sarcomas, ovarian and endometrial cancers. We also presented survival data in patients with relapsed/refractory diffuse large B-cell lymphoma treated with selinexor, along with combination data of selinexor with chemotherapy in patients with heavily pretreated acute myeloid leukemia," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "In addition, we continue to execute against the selinexor clinical development plan with the initiation of a Phase 2 study in patients with quad-refractory multiple myeloma and make steady progress enrolling patients in our other on-going later phase clinical trials in acute myeloid leukemia, diffuse large B cell lymphoma and Richter’s transformation. Furthermore, we made some important changes to certain trials based on our growing experience with selinexor. Finally, we recently met with FDA and now have a path forward for a phase 2/3 study in liposarcoma. In the second half of 2016, we look forward to reporting preliminary top-line data from our later phase clinical trials in AML, DLBCL and Richter’s transformation, as well as data from the first 80 patients in our later phase clinical trial in multiple myeloma in the middle of 2016."

Conference Call Information:
To access the conference call, please dial (855) 437-4406 (US) or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID 98056569. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of Karyopharm’s website, View Source, approximately two hours after the event.

Scientific Presentations and Publications:

• Presented positive clinical data with single-agent, oral selinexor in on-going Phase 2 and Phase 1b clinical studies across multiple solid tumors at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting including anti-tumor activity and disease control in patients with recurrent glioblastoma, advanced sarcomas, heavily pre-treated gynecological cancers and across multiple malignancies in Asian patients, including:

• anti-tumor activity, including brain penetration at clinically relevant drug levels, with a 13% overall response rate (ORR) and a 38% disease control rate (DCR) in patients with recurrent glioblastoma in an ongoing Phase 2 clinical trial;

• durable activity, including longer progression free survival (PFS) than last prior regimen, in an ongoing Phase 1b clinical study in patients with advanced sarcomas, including liposarcoma;

Targeting Disease at the Nuclear Pore

• promising anti-tumor activity or disease control across ovarian, endometrial and cervical cancers with disease control rates (DCR) of up to 62% and several patients remaining on study for up to 12 months in an ongoing Phase 2 clinical trial in patients with heavily pre-treated, progressive gynecological cancers;

• anti-tumor activity across a variety of malignancies in a Phase 1 clinical trial evaluating the activity of selinexor in Asian patients with advanced malignancies.

• Presented clinical data with oral selinexor, both as single agent and in combination with chemotherapy, in a number of hematologic malignancies including diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML) at the 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) 2015 Annual Meeting, including:

• updated survival data from an ongoing Phase 1b clinical trial of single-agent selinexor in heavily pre-treated patients with DLBCL in which patients with a response to selinexor (N=12) demonstrated a median overall survival (OS) of greater than 10 months (median not reached) and PFS was 24 months, significantly longer than those without a response (N=27; OS 3.5 months, PFS 1.2 months);

• preliminary Phase 2 results from an ongoing clinical trial of selinexor in combination with chemotherapy (idarubicin/Ara-C) in 18 evaluable patients with relapsed or refractory AML demonstrated a 56% ORR, including nine patients with complete remission (CR/CRi) and one patient with a partial remission (PR).

• Presented clinical and preclinical data with single agent, oral selinexor at the 13th International Conference on Malignant Lymphoma (ICML) in DLBCL patients with MYC, BCL2 and/or BCL6 translocations, so called "Double Hit and Triple Hit" Lymphomas — areas of significant unmet medical need associated with poor prognosis and limited standard-of-care treatment options:

• In an ongoing Phase 1 clinical trial in 14 relapsed, refractory DLBCL patients with triple, double or single hit MYC, BCL2 and/or BCL6 translocations, selinexor demonstrated clinically meaningful activity with a 43% ORR (PR or better) including two CRs, four PRs and two additional patients achieving stable disease (SD).

• In preclinical models, selinexor demonstrated potency in double hit DLBCL cell lines in vitro and in an aggressive derived xenograft (PDX) model of triple hit DLBCL, with 84% tumor growth inhibition.
Regulatory and Intellectual Property Updates:

• Karyopharm met with the FDA in July and plans to initiate a Phase 2/3 clinical trial of selinexor versus placebo to treat liposarcoma in the second half of 2015. Accrual to Karyopharm’s Phase 1b clinical trial in sarcomas, including liposarcoma, is nearly complete.

• Granted U.S. patent for KPT-350, an oral SINE compound being developed for the treatment of inflammatory and autoimmune diseases. This patent, which will expire in 2033 absent any patent term extensions, covers the composition of matter for KPT-350, as well as certain other compositions and related methods.

• Granted U.S. patent covering method of treatment using certain SINE compounds, including selinexor and verdinexor. This patent will expire in 2032 absent any patent term extensions, and the covered methods of treatment include methods for treating viral infections, inflammatory disorders and cancer.

Targeting Disease at the Nuclear Pore

Clinical Development Plans:

• Karyopharm initiated a single-arm trial in multiple myeloma called STORM, for Selinexor Treatment of Refractory Myeloma, which will initially include 80 patients. If the data from the initial 80 patients is promising, the study may be expanded to potentially support accelerated approval. Preliminary top-line data from this study are anticipated in mid-2016.

• Karyopharm is actively enrolling patients in three later-stage clinical studies evaluating selinexor: one in older patients with relapsed/refractory AML (SOPRA study), the second in patients with relapsed/refractory DLBCL (SADAL study) and the third in patients with Richter’s transformation (SIRRT study). Preliminary top-line data from all three studies are anticipated in the fourth quarter of 2016.

• Following evaluation of over 1,000 patients treated with selinexor to date, Karyopharm has determined that the recommended phase 2 dose (RP2D) for patients with the majority solid tumors and selected hematologic malignancies is 60 mg fixed dose, twice weekly; the maximum tolerated dose is ~120 mg. The recommended dose in multiple myeloma is 80 mg selinexor + 20 mg of dexamethasone together, twice weekly. Doses of up to 100 mg twice weekly will continue to be evaluated in certain indications.

• In July 2015, Karyopharm amended the SOPRA study, a Phase 2 randomized clinical trial of single-agent, oral selinexor in older patients with acute myeloid leukemia, or AML, to reduce the dose from 55mg/m2 to a fixed dose of 60mg, which corresponds to approximately 35 mg/m2. Dosing will remain twice weekly. This change was implemented based on ongoing safety and tolerability evaluations in the SOPRA study, as well as maturing data from AML patients in the Phase 1 first-in-human clinical trial of selinexor. The SOPRA study uses a two-to-one randomization of AML patients to selinexor or physician’s choice and, therefore, approximately twice as many cases of sepsis would be expected on the selinexor arm compared with the physician’s choice arm. As of the end of July 2015, there have been eight reports of sepsis in seven patients receiving selinexor 55 mg/m2 on the SOPRA study, as compared with two reports of sepsis in two patients receiving physician’s choice on that study. Therefore, although the numbers are small, and sepsis is often observed in patients with AML, the incidence of sepsis appears to be higher in the patients receiving selinexor. In addition, as our data are maturing, an apparent increase in the incidence of sepsis in patients with relapsed or refractory AML receiving high doses of selinexor twice weekly was noted in Karyopharm’s Phase 1 clinical trial in hematologic malignancies. Importantly, doses of 60mg twice weekly do not appear to be associated with any increase in sepsis or other infection-related events in patients with hematologic malignancies or solid tumors. In addition, the majority of the patients with AML in the Phase 1 study who showed a response to selinexor treatment, including patients with complete remissions, received selinexor at doses of approximately 60mg or below. As a result of the change in dose, the SOPRA study will now have an interim assessment in mid-2016 with topline data expected in the fourth quarter of 2016.

• In July 2015, Karyopharm amended the protocol of SIRRT, a Phase 2 clinical study of single-agent, oral selinexor in patients with Richter’s transformation, an aggressive form of lymphoma, to include patients with newly diagnosed Richter’s transformation. There is no standard of care for patients with Richter’s transformation and these patients have an extremely poor prognosis. As a result of these factors, and in order to improve patient accrual, in consultation with key opinion leaders in the area, Karyopharm determined that there was a compelling rationale to amend the SIRRT protocol to include patients who had not yet received chemotherapy to treat Richter’s transformation. Karyopharm is now implementing the revised protocol across SIRRT study sites in the United States and Europe.

• Karyopharm expects to commence the STOMP ("Selinexor and Backbone Treatments of Multiple Myeloma Patients") study in the third quarter with support from Myeloma Canada. In this multi-arm clinical study, Karyopharm plans to evaluate the combination of selinexor and low dose dexamethasone with backbone therapies including bortezomib, pomalidomide or lenalidomide in patients with multiple myeloma. Selinexor and low dose dexamethasone is already being combined with Kyprolis in an Investigator Sponsored Trial, where promising preliminary data were presented at ASH (Free ASH Whitepaper) 2014.

Targeting Disease at the Nuclear Pore

• Karyopharm is currently conducting company-sponsored trials of single-agent selinexor in four solid tumor indications. At ASCO (Free ASCO Whitepaper) 2015, Karyopharm reported responses and disease control in patients with heavily pretreated gynecologic malignancies (SIGN study) and in recurrent glioblastoma multiforme (KING study); accrual to these studies is continuing. Karyopharm is also continuing to accrue patients to the SHIP study, a phase 2 study of selinexor in previously treated, hormone-refractory prostate cancer. The fourth phase 2 solid tumor study, the STARRS study, involves patients with relapsed or refractory squamous cell tumors. Enrollment to the head and neck cohort of this study has been completed and, due to very slow accrual in the lung and esophageal squamous carcinoma cohorts, Karyopharm is terminating further enrollment to these arms and finalizing the study. Additional trials with selinexor in combination with various chemotherapies are ongoing and may include patients with squamous cell carcinomas.

• In addition, a number of investigator-sponsored (ISTs) or company-sponsored clinical studies evaluating the potential of selinexor in combination with either chemotherapy or targeted agents are currently ongoing or planned.

Second Quarter June 30, 2015 Financial Results
Cash, cash equivalents and investments as of June 30, 2015, including restricted cash, totaled $256.0 million, compared to $285.3 million as of March 31, 2015.

For the quarter ended June 30, 2015, research and development expense was $27.0 million compared to $13.2 million for the quarter ended June 30, 2014. For the quarter ended June 30, 2015, general and administrative expense was $6.2 million compared to $3.3 million for the quarter ended June 30, 2014. The increase in research and development expenses resulted primarily from the increase in expenses related to the continued clinical development of selinexor. The increase in general and administrative expense resulted primarily from the costs of being a public company and an increase in stock-based compensation.
Karyopharm reported a net loss of $32.7 million, or $0.92 per share, for the quarter ended June 30, 2015, compared to a net loss of $16.4 million, or $0.55 per share, for the quarter ended June 30, 2014. Net loss includes stock-based compensation expense of $4.5 million and $3.9 million for the quarters ended June 30, 2015 and June 30, 2014, respectively.

Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents will fund its research and development programs and operations into 2018, including moving the four later-stage clinical studies to their next data inflection points. Karyopharm expects to end 2015 with greater than $200 million in cash, cash equivalents and investments.
"Karyopharm continues to maintain a very strong balance sheet, with approximately $256M in cash as of the end of the second quarter of 2015," said Justin Renz, Executive Vice President, Chief Financial Officer & Treasurer. "As for financial guidance this year, we remain on track to end 2015 with greater than $200M in cash."

On August 10, 2015 Intrexon Corporation (NYSE: XON), a leader in synthetic biology, reported its second quarter and first half results for 2015 (Press release, Intrexon, AUG 10, 2015, View Source;p=RssLanding&cat=news&id=2078523 [SID:1234507150]).

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Business Highlights and Recent Developments:

During the second quarter, Intrexon’s exclusive collaboration and license agreement with the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, to develop and commercialize chimeric antigen receptor T-cell (CAR-T) cancer therapies became effective, resulting in the receipt of $115 million, 50% of which is payable to ZIOPHARM Oncology, Inc., as an upfront fee in July 2015. Focused on the generation of leading-edge products that empower the immune system in a regulated manner, the collaboration’s first two CAR-T targets of interest have been selected and Intrexon has initiated research and development efforts on these programs;

Granted a special stock dividend of ZIOPHARM Oncology, Inc. (NASDAQ: ZIOP) shares owned by Intrexon to its shareholders valued at approximately $172 million at the time of distribution. Holders of Intrexon common stock received 0.162203 shares of ZIOPHARM common stock at $9.67 per share with respect to each outstanding share of Intrexon common stock they owned;
Announced a Cooperative Research and Development Agreement with the National Cancer Institute (NCI). The principal goal is to develop and evaluate improved adoptive cell transfer-based immunotherapies (ACT) using NCI proprietary methods for the identification of autologous peripheral blood lymphocytes with naturally occurring endogenous anti-tumor activity combined with the RheoSwitch Therapeutic System for introducing spatially and temporally controlled interleukin-12 (IL-12) expression in ACT/PBL/IL-12 for the treatment of patients with solid tumor malignancies;

Completed the acquisition of Okanagan Specialty Fruits, the pioneering agricultural company behind the Arctic apple, the world’s first non-browning apple without the use of any flavor-altering chemical or antioxidant additives;

Entered into a multi-year collaboration with an investment fund sponsored by Harvest Capital Strategies, LLC. The fund is dedicated to the inventions and discoveries of Intrexon and will have the exclusive rights of first-look and first negotiation for Intrexon’s investment proposals suitable for pursuit by a startup. The fund will be complementary to Intrexon’s ongoing programs and will not prohibit the Company’s ability to execute other collaborations and joint ventures;

In collaboration with Fibrocell Science, Inc. (NASDAQ: FCSC) announced submission of an Investigational New Drug Application to the U.S. Food and Drug Administration for FCX-007 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a debilitating genetic skin disorder caused by a mutation in the gene encoding type VII collagen (COL7), a protein that forms anchoring fibrils which hold together the layers of skin. Additionally, the companies reported positive proof-of-concept data from in vivo pre-clinical studies for FCX-007. Fibrocell expects to initiate a Phase I/II clinical trial by year-end to evaluate the safety, mechanism of action, and efficacy of FCX-007;

Expanded relationship with Oragenics (NYSE MKT: OGEN) through a new Exclusive Channel Collaboration (ECC) to pursue development of biotherapeutics for oral mucositis and other diseases of the oral cavity, throat, and esophagus, including clinical advancement of ActoBiotics AG013 for the treatment of oral mucositis; and

In conjunction with Oragenics, announced selection of lead clinical candidate for the lantibiotics program and reported positive in vivo efficacy data in critical animal study on multiple compounds from Oragenics’ Mutacin 1140 platform. Lantibiotics are a class of antibiotics with a novel mechanism of action active against a broad spectrum of Gram-positive bacteria, including multi-drug resistant infectious bacteria, which could provide an important new tool in the fight against global bacterial antibiotic resistance.

Second Quarter Financial Highlights:

Total revenues of $44.9 million, an increase of 281% over the second quarter of 2014;
Net loss of $40.7 million attributable to Intrexon, or $(0.37) per basic share;
Excluding the special stock dividend of ZIOPHARM Oncology, Inc. shares, Pro Forma Net Income Attributable to Intrexon during the second quarter would have been of $0.9 million, or $0.01 per basic share;
Adjusted EBITDA of $54.4 million, or $0.50 per basic share; and
Cash consideration received for reimbursement of research and development services, Cost Recovery, covered 60% of cash operating expenses (exclusive of operating expenses of consolidated subsidiaries).

First Half Financial Highlights:

Total revenues of $78.7 million, an increase of 301% over the first half of 2014;
Net loss of $13.6 million attributable to Intrexon, or $(0.13) per basic share;
Excluding the special stock dividend of ZIOPHARM Oncology, Inc. shares, Pro Forma Net Income Attributable to Intrexon during the first half would have been $28.0 million, or $0.26 per basic share;
Adjusted EBITDA of $39.8 million, or $0.37 per basic share; and
Total consideration received for technology access fees and reimbursement of research and development services covered 187% of cash operating expenses (exclusive of operating expenses of consolidated subsidiaries).

"We continue satisfactorily to balance contemporary inputs to outputs while advancing a growing portfolio of programs that should provide significant and unburdened contribution to our bottom line," commented Randal J. Kirk, Chairman and Chief Executive Officer of Intrexon. "The scalability of our technology platforms and our organizational model are allowing us to grow our company rapidly across an ever diversifying array of great product candidates while we add important new talent to our team. That we can execute such an ambitious plan while also making acquisitions that provide positions of genuine industrial leadership is a testament to the great team that so zealously advances our mission to ‘power the bioindustrial revolution.’"

Second Quarter 2015 Financial Results Compared to Prior Year Period

Total revenues were $44.9 million for the quarter ended June 30, 2015 compared to $11.8 million for the quarter ended June 30, 2014, an increase of $33.1 million, or 281%. Product revenue includes $12.6 million from the sale of pregnant cows, live calves and the sale of livestock used in production. Service revenue totaling $11.6 million relates to the provision of in vitro fertilization and embryo transfer services performed. Collaboration revenues increased $5.4 million due to (i) the recognition of deferred revenue for upfront payments received from our license and collaboration agreement with the biopharmaceutical business of Merck KGaA, which became effective in May 2015, and from collaborations signed by us between July 1, 2014 and June 30, 2015, (ii) the recognition of research and development services performed by us pursuant to these new collaborations, and (iii) increased research and development services performed by us related to collaboration programs in effect prior to July 1, 2014 as a result of progression of current programs and the initiation of new programs with these collaborators.

Total operating expenses were $62.3 million for the quarter ended June 30, 2015 compared to $29.9 million for the quarter ended June 30, 2014, an increase of $32.4 million, or 108%. Research and development expenses were $20.4 million for the quarter ended June 30, 2015 compared to $14.4 million for the quarter ended June 30, 2014, an increase of $5.9 million, or 41%. Salaries, benefits and other personnel costs increased $2.5 million due to (i) increases in research and development headcount to support the new collaborations discussed above, and (ii) compensation expenses related to performance and retention incentives for research and development employees. Lab supplies and consultants increased $2.1 million due to the increased level of research and development services provided to our collaborators. Selling, general and administrative expenses were $23.7 million for the quarter ended June 30, 2015 compared to $15.4 million for the quarter ended June 30, 2014, an increase of $8.3 million, or 54%. Salaries, benefits and other personnel costs increased $5.5 million due to (i) the inclusion of selling, general and administrative employees of companies we have acquired since July 1, 2014, including Trans Ova and ActoGeniX, and (ii) compensation expenses related to performance and retention incentives for general and administrative employees. Depreciation and amortization increased $0.8 million primarily as a result of property and equipment and intangible assets acquired from Trans Ova. Total operating expenses for the quarter ended June 30, 2015 also include $18.2 million of products and services costs which primarily consist of employee compensation costs, livestock, feed, drug supplies and facility charges related to the production of such products and services.

Total other expense, net, was $21.0 million for the quarter ended June 30, 2015 compared to $33.8 million for the quarter ended June 30, 2014, a decrease of $12.8 million, or 38%. This decrease was primarily related to the changes in the value of our securities portfolio, including a realized gain of $81.4 million which resulted from the special stock dividend of all of our shares of ZIOPHARM to our shareholders in June 2015.

First Half 2015 Financial Results Compared to Prior Year Period

Total revenues were $78.7 million for the six months ended June 30, 2015 compared to $19.6 million for the six months ended June 30, 2014, an increase of $59.1 million, or 302%. Product revenue includes $20.1 million from the sale of pregnant cows, live calves and the sale of livestock used in production. Service revenue totaling $20.0 million relates to the provision of in vitro fertilization and embryo transfer services performed. Collaboration revenues increased $12.4 million due to (i) the recognition of deferred revenue for upfront payments received from our license and collaboration agreement with the biopharmaceutical business of Merck KGaA, which became effective in May 2015, collaborations signed by us between July 1, 2014 and June 30, 2015 and our collaboration with Intrexon Energy Partners, which was signed in March 2014, (ii) recognition of research and development services performed by us pursuant to these new collaborations, and (iii) increased research and development services performed by us for collaborations in effect prior to July 1, 2014 as a result of the progression of current programs and the initiation of new programs with these collaborators.

Total operating expenses were $183.3 million for the six months ended June 30, 2015 compared to $55.6 million for the six months ended June 30, 2014, an increase of $127.7 million, or 230%. Research and development expenses were $99.7 million for the six months ended June 30, 2015 compared to $26.5 million for the six months ended June 30, 2014, an increase of $73.2 million, or 276%. In January 2015, we issued 2,100,085 shares of our common stock valued at $59.6 million to the University of Texas MD Anderson Cancer Center, or MD Anderson, in exchange for an exclusive license to certain technologies owned by MD Anderson. Salaries, benefits and other personnel costs increased $5.9 million due to (i) increases in research and development headcount to support the new collaborations discussed above, and (ii) compensation expenses related to performance and retention incentives for research and development employees. Lab supplies and consultants expenses increased $4.0 million as a result of the increased level of research and development services provided to our collaborators. Selling, general and administrative expenses were $51.3 million for the six months ended June 30, 2015 compared to $29.0 million for the six months ended June 30, 2014, an increase of $22.3 million, or 77%. Salaries, benefits and other personnel costs increased $13.4 million due to (i) the inclusion of selling, general and administrative employees of companies we have acquired since July 1, 2014, including Trans Ova and ActoGeniX, and (ii) compensation expenses related to performance and retention incentives for general and administrative employees. Stock-based compensation expenses for the annual options granted to our non-employee directors, pursuant to our non-employee director compensation policy, increased $1.0 million due to a higher grant-date fair value in 2015 compared to 2014. Legal and professional expenses increased $2.7 million primarily due to costs associated with acquisitions, the license agreement with MD Anderson, the January 2015 public securities offering and other business development activity. Depreciation and amortization increased $1.6 million primarily as a result of property and equipment and intangible assets acquired from Trans Ova. Total operating expenses for the six months ended June 30, 2015 also include $32.1 million of products and services costs which primarily consist of employee compensation costs, livestock, feed, drug supplies and facility charges related to the production of such products and services.

Total other income, net, was $94.7 million for the six months ended June 30, 2015 compared to total other expense, net, of $11.8 million for the six months ended June 30, 2014, an increase of $106.5 million, or 903%. This increase was primarily related to the changes in the value of our securities portfolio, including a realized gain of $81.4 million which resulted from the special stock dividend of all of our shares of ZIOPHARM to our shareholders in June 2015.

On August 10, 2015 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported financial results for the quarter ended June 30, 2015 (Press release, Inovio, AUG 10, 2015, View Source [SID:1234507149]).

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Total revenue was $5.3 million and $10.5 million for the three and six months ended June 30, 2015, compared to $3.8 million and $6.2 million for the same periods in 2014.

Total operating expenses were $20.4 million and $33.9 million for the three and six months ended June 30, 2015, compared to $14.0 million and $26.3 million for the same periods in 2014.

The net loss attributable to common stockholders for the three and six months ended June 30, 2015, was $6.2 million, or $0.09 per share, and $16.8 million, or $0.26 per share, compared to $10.7 million, or $0.18 per share, and $21.5 million, or $0.37 per share, for the same periods in 2014.

Revenue

The increase in revenue was primarily due to the $3.0 million milestone payment earned in the second quarter 2015 under our partnership agreement with Roche.

Operating Expenses

Research and development expenses for the three and six months ended June 30, 2015, were $16.7 million and $26.1 million, compared to $9.6 million and $17.8 million for the same periods in 2014. The increase for the three and six-month periods was primarily related to increased investment in our product development programs. General and administrative expenses for the three and six months ended June 30, 2015, were $4.7 million and $8.8 million versus $4.3 million and $8.5 million for the same periods in 2014.

Capital Resources

As of June 30, 2015, cash and short-term investments were $154.6 million compared with $93.6 million as of December 31, 2014. At quarter end the company had 71.8 million shares outstanding and 78.9 million fully diluted.

On May 5, 2015, the Company closed an underwritten public offering of 10,925,000 shares of the Company’s common stock, including 1,425,000 shares of common stock issued pursuant to the underwriter’s exercise of its option, at the public offering price of $8.00 per share. The gross proceeds of this offering were $87.4 million. Net proceeds to the Company, after deducting the underwriter’s discounts and commission and other offering expenses, were $81.9 million.

We intend to use the net proceeds received from the sale of our common stock for general corporate purposes, including clinical trial expenses, research and development expenses, general and administrative expenses, manufacturing expenses and potential acquisitions of companies and technologies that complement our business.

Based on management’s projections and analysis, the Company believes that cash and short-term investments meet its planned working capital requirements through the end of 2018.

Inovio’s balance sheet and statement of operations are provided below. Form 10-Q providing the complete 2015 second quarter financial report can be found at: View Source

Corporate Update

Corporate Development

On August 7, 2015, Inovio entered into a strategic cancer vaccine collaboration and license agreement with MedImmune, the global biologics research and development arm of AstraZeneca. Under the agreement, MedImmune acquired exclusive rights to Inovio’s INO-3112 immunotherapy, which targets cancers caused by human papillomavirus (HPV) types 16 and 18. MedImmune intends to study INO-3112 in combination with selected immunotherapy molecules within its pipeline in HPV-driven cancers. Emerging evidence suggests that the benefits from immuno-oncology molecules, such as those in MedImmune’s portfolio, can be enhanced when they are used in combination with cancer vaccines that generate tumor-specific T-cells.

Under the terms of the agreement, MedImmune will make an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.

Within the broader collaboration, Inovio and MedImmune will develop up to two additional DNA-based cancer vaccine products not included in Inovio’s current product pipeline, which MedImmune will have the exclusive rights to develop and commercialize. Inovio will receive development, regulatory and commercialization milestone payments and will be eligible to receive royalties on worldwide net sales for these additional cancer vaccine products.

This is Inovio’s second major partnership with a large pharmaceutical company, adding to its existing license agreement with Roche for Inovio’s INO-1800 hepatitis B immunotherapy. The initiation of a phase I trial for INO-1800 in April triggered a $3 million milestone payment from Roche.

We initiated a partnership with Europe’s largest cancer organization, the European Organization for Research and Treatment of Cancer (EORTC), to evaluate INO-3112 in combination with traditional chemo-radiotherapy for the treatment of patients with locally advanced stage cervical cancer. The primary endpoint of this phase II study is to evaluate progression free survival at 18 months. It is expected to begin in 2016 and will be part of MedImmune’s development plans.

Under an award worth potentially $45 million from the Defense Advanced Research Projects Agency (DARPA), Inovio and collaborators are advancing multiple treatment and prevention approaches against Ebola. These approaches include DNA-based monoclonal antibody technology, protein-based therapeutic monoclonal antibodies, and DNA-based vaccines.

We will advance our DNA vaccine for Middle East Respiratory Syndrome (MERS) into a phase I clinical trial in healthy volunteers in a collaboration with GeneOne Life Science Inc. GeneOne will conduct and fund the clinical study, expected to start by year end, in return for milestone-based co-ownership of this immunotherapy.

Inovio continues its corporate development efforts to secure grants, collaborations, and partnerships to help advance its SynCon immunotherapy and vaccine products.

Clinical Development

Our manuscript detailing the broad study findings of our phase II study of VGX-3100 in patients with high-grade cervical dysplasia (CIN 2/3) has been accepted by a top peer-reviewed medical journal.

We continue preparations to launch our planned phase III registration study of VGX-3100 in early 2016. Necessary steps include scaling from pilot-scale to commercial-level production of our immunotherapy product and delivery devices, significant projects with important quality assurance standards to maintain. We expect our end-of-phase-II meeting with the FDA, which will review our phase II data and proposed phase III clinical trial design, to take place by year end.

As part of our expanding franchise targeting all HPV-associated pre-cancers and cancers, we reported preliminary data from our first cancer study, a head & neck cancer trial, showing that INO-3112 (VGX-3100 plus Inovio’s IL-12 based immune activator) generated strong CD8+ T cell responses in 3 of 4 patients. This study, along with our ongoing cervical cancer phase I study of INO-3112, will now be part of MedImmune’s development plans.

Subsequent to the quarter we launched our phase I study of INO-5150, our SynCon immunotherapy targeting prostate-specific membrane antigen and prostate-specific antigen, in men with biochemically relapsed prostate cancer. This study is evaluating the safety, tolerability, and immunogenicity of INO-5150 alone or in combination with INO-9012, Inovio’s DNA-based IL-12 immune activator.

We initiated with our partner Roche a phase I trial for our hepatitis B immunotherapy, INO-1800. This randomized, open-label, active-controlled, dose escalation study is evaluating the safety, tolerability, and immunogenicity of Inovio’s hepatitis B immunotherapy alone or in combination with Inovio’s IL-12-based immune activator.

The company initiated a phase I trial to evaluate its Ebola immunotherapy and we expect the HIV Vaccine Trials Network to initiate a phase I study of PENNVAX-GP in 2H 2015.

On August 10, 2015 Inovio Pharmaceuticals (Nasdaq:INO) reported that it has entered into a license agreement and collaboration with MedImmune, the global biologics research and development arm of AstraZeneca (Press release, Inovio, AUG 10, 2015, View Source [SID:1234507147]).

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Under the agreement, MedImmune will acquire exclusive rights to Inovio’s INO-3112 immunotherapy, which targets cancers caused by human papillomavirus (HPV) types 16 and 18. INO-3112, which is in phase I/II clinical trials for cervical and head and neck cancers, works by generating killer T-cell responses that are able to destroy HPV 16- and 18-driven tumors. These HPV types are responsible for more than 70 percent of cervical pre-cancers and cancers.

MedImmune intends to study INO-3112 in combination with selected immunotherapy molecules within its pipeline in HPV-driven cancers. Emerging evidence suggests that the benefits from immuno-oncology molecules, such as those in MedImmune’s portfolio, can be enhanced when they are used in combination with cancer vaccines that generate tumor-specific T-cells.

Under the terms of the agreement, MedImmune will make an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.

Within the broader collaboration, MedImmune and Inovio will develop up to two additional DNA-based cancer vaccine products not included in Inovio’s current product pipeline, which MedImmune will have the exclusive rights to develop and commercialize. Inovio will receive development, regulatory and commercialization milestone payments and will be eligible to receive royalties on worldwide net sales for these additional cancer vaccine products.

Dr. David Berman, Senior Vice President and Head of the Oncology Innovative Medicines unit, MedImmune, said: "Today’s collaboration with Inovio leverages our deep internal expertise in the use of vaccines to drive antigen-specific T-cell responses. The unique combination of our broad immuno-oncology portfolio with Inovio’s T-cell-activating INO-3112, which enhances cancer specific killer T-cells, has the potential to deliver real clinical benefits for patients."

Dr. J. Joseph Kim, President and CEO, Inovio, said: "Our licensing partnership with MedImmune represents an important step in executing our immuno-oncology combination strategy and advancing Inovio’s cancer vaccine R&D pipeline with a leading cancer immunotherapy company. INO-3112 is progressing, with positive interim data generated in an Inovio-initiated phase I study. We appreciate MedImmune’s recognition of our ability to activate best-in-class killer T-cells in vivo and look forward to working with them on this collaboration."

Today’s agreement builds on the existing partnership between Inovio and MedImmune on two research and development collaborations in the infectious disease area. Both efforts are funded by the Defense Advanced Research Projects Agency (DARPA) and support R&D focused on Ebola, influenza, and bacterial infections. MedImmune has a strong heritage in infectious disease and vaccine innovation, having developed the first monoclonal antibody approved by the US Food & Drug Administration for the prevention of an infectious disease and the technology that led to the creation of an HPV vaccine.

About INO-3112

Inovio’s SynCon DNA-based immunotherapies help the immune system activate disease-specific killer T cells to fight a targeted disease. HPV, the most pervasive sexually transmitted virus, causes numerous pre-cancers and cancers. Inovio’s HPV immunotherapy called INO-3112 targets disease associated with the high-risk HPV types 16 and 18, which are responsible for over 70% of cervical pre-cancers and cancers. INO-3112 combines Inovio’s VGX-3100, its immunotherapy targeting HPV-caused diseases, with its DNA-based immune activator encoded for IL-12. INO-3112 is in three clinical studies for cervical and head and neck cancers.

Earlier this year, Inovio reported preliminary data showing that INO-3112 generated significant antigen-specific CD8+ T cell responses in 3 of 4 patients with head and neck cancer associated with human papillomavirus (HPV) types 16 and 18. These positive results represent the first study and first report of antigen-specific T cell immune responses generated in cancer patients after treatment with a DNA immunotherapy.

Previously in a phase II efficacy trial, treatment with VGX-3100 resulted in histopathological regression of late-stage cervical dysplasia to early stage or no disease, meeting the study’s primary endpoint. In addition, the trial demonstrated clearance of the HPV virus in conjunction with regression of cervical lesions, meeting the secondary endpoint. Robust T-cell activity was observed in subjects who received VGX-3100 compared to those who received placebo.

On August 10, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported company highlights and financial results for the second quarter ended June 30, 2015 (Press release, Ignyta, AUG 10, 2015, View Source [SID:1234507143]).

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"Since the beginning of the second quarter of 2015, we have continued to make important strides toward our goal of becoming a leading precision oncology biotechnology company that can provide compelling treatment options to cancer patients with unmet needs," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We made strong progress on our lead product candidate, entrectinib, announcing promising data at ASCO (Free ASCO Whitepaper) from our two Phase I clinical trials, releasing our proprietary next-generation sequencing assay to support our potentially registration-enabling STARTRK-2 Phase 2 clinical trial, and kicking off a collaboration with UCSF to study entrectinib in melanoma. We are also starting to gain good momentum in advancing the former Teva assets we acquired only a quarter earlier, as exemplified by the FDA’s clearance of our IND for RXDX-107, for which we are preparing to initiate a Phase 1/1b clinical trial. We also strengthened our balance sheet by raising gross proceeds of approximately $75 million in an underwritten public offering of our common stock, and we continued to expand our team with incredibly talented people."

Company Highlights

Presentation of Entrectinib Clinical Data at ASCO (Free ASCO Whitepaper)

In June 2015, Ignyta announced that interim results from the company’s two Phase 1 clinical trials of entrectinib were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois.

The clinical trials included the ALKA-372-001 study and the STARTRK-1 study, which is the first of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." Both trials were designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant molecular alterations: NTRK1 (encoding TrkA), ROS1 or ALK for ALKA-372-001 and NTRK1/2/3 (encoding TrkA/TrkB/TrkC), ROS1 or ALK for STARTRK-1.

As of the May 1, 2015, data cut-off for the presentation, the findings showed:

A total of 67 patients with a range of solid tumors had been dosed across both clinical trials;
Entrectinib was well tolerated to date, with no treatment-related serious adverse events. Other safety findings included:
In the ALKA-372-001 study, two Grade 3 treatment-related adverse events were observed: fatigue and muscle weakness, each of which subsided with dose reduction. The most frequent adverse events were paresthesia, nausea, myalgia, asthenia, dysgeusia, and vomiting;

In the STARTRK-1 study, three Grade 3 treatment-related adverse events were observed: neutropenia, which resolved with dose reduction, and two dose-limiting toxicities of reversible cognitive impairment and fatigue, both of which resolved upon study drug interruption. The most frequent adverse events were fatigue, dysgeusia, constipation, nausea, and paresthesia;

Pharmacokinetic measurements showed dose-proportional increases across the daily dosing regimens evaluated, with a half-life compatible with once-daily dosing;

The body surface area (BSA)-based recommended Phase 2 dose was determined to be 400 mg/m2 once per day (QD); both studies are continuing in order to determine a fixed daily dose regimen;

11 patients across both clinical trials met the company’s expected Phase 2 eligibility criteria, which include:
Presence of NTRK1/2/3, ROS1 or ALK fusions, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);

ALK inhibitor and/or ROS1 inhibitor naïve; and

Treatment at or above the recommended Phase 2 dose of 400 mg/m2;

The response rate in the 11 patients that met these criteria across both studies was 91% (10 of 11 responses as assessed by the clinical sites), with 9 patients remaining on study treatment with durable responses of up to 16 treatment cycles. The responses included:

3 of 3 responses in patients with NTRK1/2/3 fusions, including patients with non-small cell lung cancer (NSCLC), colorectal cancer and acinic cell cancer;

5 of 6 responses, including one complete response, in patients with ROS1 fusions, all of which were in NSCLC; and
2 of 2 responses in patients with ALK fusions, including one NSCLC patient and one patient with another solid tumor.

Release for Clinical Use of Proprietary NGS Clinical Trial Assay

In June 2015, the company announced the release for clinical use of its first clinical trial assay to support patient identification and enrollment into its STARTRK clinical development program for entrectinib. The proprietary assay was co-developed with ArcherDx and validated within Ignyta’s own CLIA-registered, QSR-compliant diagnostic lab in San Diego. This lab will utilize this assay in acting as the central testing lab for patient screening for the STARTRK-2 Phase 2 clinical study of entrectinib.

Entrectinib Collaboration with UCSF

In July 2015, the company announced a clinical collaboration with the University of California, San Francisco (UCSF), under which UCSF will study entrectinib in a proof-of-concept clinical trial in cancer patients with metastatic melanoma that is positive for activating alterations to NTRK1/2/3 (encoding TrkA/TrkB/TrkC) or ROS1.

The study is a multicenter, open label umbrella trial designed by UCSF to obtain proof-of-concept data in patients with metastatic melanoma that is positive for molecular alterations in specific tyrosine kinase receptors. UCSF will exclusively use entrectinib for patients enrolled in the clinical trial having activating molecular alterations to NTRK1/2/3 or ROS1.

Clearance of Investigational New Drug (IND) Application for RXDX-107

In July 2015, Ignyta announced that the U.S. Food and Drug Administration (FDA) cleared the IND for Ignyta’s new chemical entity RXDX-107, a next-generation alkyl ester of bendamustine encapsulated in human serum albumin (HSA) to form nanoparticles.

Under this IND, the company intends to initiate a new Phase 1/1b, multicenter, open-label clinical trial of RXDX-107 in adult patients. This dose-escalation study is designed to determine the MTD, RP2D, tolerability, pharmacokinetics and preliminary clinical activity of RXDX-107 in patients with locally advanced or metastatic solid tumors.

Financing

In June 2015, the company issued an aggregate of 4,285,714 shares of its common stock in an underwritten public offering at a purchase price of $17.50 per share, which resulted in aggregate gross proceeds of approximately $75 million.

Enhancement of Leadership Capacity

In July 2015, Ignyta announced that Bernard Parker joined the company as its Chief Commercial Officer, bringing to the company broad commercial oncology experience from a variety of senior roles spanning sales, marketing, reimbursement, global brand management and regional business unit leadership at several leading pharmaceutical companies. Mr. Parker’s previous experience includes serving as Head of the EMEA Pharmaceuticals Franchise for the Alcon division of Novartis; as Global Brand Director, Biopharmaceuticals Portfolio for the Sandoz division of Novartis; as a management consultant at Bain & Company; and in various marketing and sales roles at Amgen, Pfizer and Parke-Davis.

Second Quarter 2015 Financial Results

For the second quarter of 2015, net loss was $13.1 million, or $0.51 per share, compared with $5.4 million, or $0.28 per share, for the second quarter of 2014.

Ignyta did not record any revenue for the three months ended June 30, 2015. Ignyta recorded revenue of $150,000 for the three months ended June 30, 2014, which consisted of a one-time service fee for research services conducted in the second quarter of 2014.

Research and development expenses for the second quarter of 2015 were $8.8 million, compared with $3.6 million for the second quarter of 2014. The increase was primarily due to an increase in activities relating to development of entrectinib and the company’s other product candidates, including the assets acquired from Teva Pharmaceutical Industries Ltd. in March 2015. The increase between periods was also due to personnel expenses related to hiring and engaging additional employees and consultants to help advance the company’s product candidates, facilities related expenses as a result of the expansion of the company’s leased facilities space and expenses incurred in connection with the Teva asset acquisition.

General and administrative expenses were $3.9 million for second quarter of 2015, compared with $2.0 million for second quarter of 2014. The increase was primarily caused by increases in personnel costs and investor relations, audit, legal and intellectual property costs.

At June 30, 2015, the company had cash, cash equivalents and available-for-sale securities totaling $166.4 million and current and long-term debt of approximately $21.0 million. At December 31, 2014, the company had cash, cash equivalents and available-for-sale securities totaling $76.6 million and current and long-term debt of approximately $21.0 million.