On August 1, 2017 Incyte Corporation (Nasdaq: INCY) reported 2017 second-quarter financial results, highlighting strong revenue growth driven by increased sales of Jakafi (ruxolitinib) in the U.S. and Iclusig (ponatinib) in Europe, and royalties from ex-U.S. sales of Jakavi (ruxolitinib) by Novartis and Olumiant (baricitinib) by Lilly (Press release, Incyte, AUG 1, 2017, View Source [SID1234519968]).

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Recent highlights also include the initiation of two pivotal studies (ruxolitinib for treatment-refractory chronic graft versus host disease (GVHD); itacitinib for steroid-naïve acute GVHD), and the presentation of multiple data sets at ASCO (Free ASCO Whitepaper) 2017 supporting the expansion of the pivotal trial program for epacadostat.

"Revenue growth from Jakafi and Iclusig continues to be very robust, driven by strong demand, and we have also made significant progress across our clinical portfolio. As we look forward to the second half of 2017, we anticipate the publication of important data from our development candidates, as well as the initiation of multiple additional pivotal combination studies with epacadostat," stated Hervé Hoppenot, Chief Executive Officer, Incyte. "Investment in innovation has created significant value for Incyte, our stakeholders and for the patients that our products treat. With strong revenue growth, a broad clinical development portfolio, comprehensive drug discovery capabilities and an expanded geographic footprint which now includes the U.S., Europe and Japan, we believe that we are well positioned for long-term value creation."

Portfolio Update
Cancer – Targeted Therapies
In July, the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for myeloproliferative neoplasms (MPNs) were published, and now include Jakafi as a recommended treatment for patients with myelofibrosis and patients with polycythemia vera who have had an inadequate response to first-line therapies, such as hydroxyurea.

In June, REACH3, a Phase 3 trial of ruxolitinib as a treatment for patients with steroid-refractory chronic GVHD, was initiated. REACH3 is being conducted in collaboration with Novartis.
RESET-272, the double-blind, randomized pivotal trial of ruxolitinib versus anagrelide for the treatment of patients with essential thrombocythemia who are resistant to or intolerant of hydroxyurea, is now open for enrollment.
GRAVITAS-301, the Phase 3 trial of itacitinib, Incyte’s selective JAK1 inhibitor, in patients with treatment-naïve acute GVHD, began dosing in July.

Following a review of the clinical profiles of Incyte’s two BRD inhibitors, INCB54329 and INCB57643, including data expected to be presented at medical meetings in the second half of 2017, the Company intends to focus future development efforts on INCB57643.
In June, Incyte initiated the Phase 1/2 dose-escalation trial of its FGFR4 inhibitor, INCB62079, in patients with hepatocellular carcinoma.

Indication Status Update
Ruxolitinib (JAK1/JAK2) Steroid-refractory acute GVHD Pivotal Phase 2 (REACH1) and Phase 3 (REACH2)
Ruxolitinib (JAK1/JAK2) Steroid-refractory chronic GVHD Phase 3 (REACH3)
Ruxolitinib (JAK1/JAK2) Essential thrombocythemia Pivotal Phase 2 (RESET-272) open for enrollment
Itacitinib (JAK1) Treatment-naïve acute GVHD Phase 3 (GRAVITAS-301)
Itacitinib (JAK1) Non-small cell lung cancer Phase 1/2 in combination with osimertinib (EGFR)
INCB52793 (JAK1) Advanced malignancies Phase 1/2 dose-escalation
INCB50465 (PI3Kδ) Diffuse large B-cell lymphoma Phase 2 (CITADEL-202)
INCB54828 (FGFR1/2/3) Bladder cancer, cholangiocarcinoma; 8p11 MPNs
Phase 2 (FIGHT-201, FIGHT-202, FIGHT-203)
INCB57643 (BRD) Advanced malignancies Phase 1/2 dose-escalation
INCB53914 (PIM) Advanced malignancies Phase 1/2 dose-escalation
INCB59872 (LSD1) Acute myeloid leukemia, small cell lung cancer Phase 1/2 dose-escalation
INCB62079 (FGFR4) Hepatocellular carcinoma Phase 1/2 dose-escalation

Cancer – Immune Therapies
At ASCO (Free ASCO Whitepaper) 2017 in June, new data from the ECHO-202 and ECHO-204 Phase 1/2 trials of epacadostat plus PD-1 inhibitors were presented in multiple tumor types. These data formed the basis of the decisions to proceed into multiple Phase 3 trials, in collaboration with each of Merck and Bristol-Myers Squibb, respectively, as announced earlier this year.

In June 2017, Incyte and Roche/Genentech decided to close the ECHO-110 trial of epacadostat plus atezolizumab to further enrollment because of slow study recruitment.

Indication Status Update
Epacadostat (IDO1) Unresectable or metastatic melanoma Phase 3 (ECHO-301) in combination with pembrolizumab (PD-1)
Epacadostat (IDO1) NSCLC, renal, bladder and head & neck cancer Phase 3 in combination with pembrolizumab (PD-1) expected to begin in 2017
Epacadostat (IDO1) NSCLC, head & neck cancer Phase 3 in combination with nivolumab (PD-1) expected to begin in 2017
Epacadostat (IDO1) Multiple tumor types Phase 2 (ECHO-202) expansion cohorts in combination with pembrolizumab (PD-1)
Epacadostat (IDO1) Multiple tumor types Phase 2 (ECHO-204) expansion cohorts in combination with nivolumab (PD-1)
Epacadostat (IDO1) Multiple tumor types Phase 2 (ECHO-203) expansion cohorts in combination with durvalumab (PD-L1)
INCB01158 (ARG)1 Solid tumors Phase 1/2 dose-escalation
INCSHR1210 (PD-1)2 Solid tumors Phase 1/2 dose-escalation completed; enrollment suspended
INCAGN1876 (GITR)3 Solid tumors Phase 1/2 dose-escalation
INCAGN1949 (OX40)3 Solid tumors Phase 1/2 dose-escalation
PD-1 platform study Solid tumors Phase 1/2, pembrolizumab (PD-1) in combination with itacitinib (JAK1) or INCB50465 (PI3Kδ)
JAK1 platform study Solid tumors Phase 1/2, itacitinib (JAK1) in combination with epacadostat (IDO1) or INCB50465 (PI3Kδ)

Notes:
1) INCB01158 co-developed with Calithera
2) INCSHR1210 licensed from Hengrui
3) INCAGN1876 & INCAGN1949 from discovery alliance with Agenus

Non-oncology
In June, Incyte initiated a Phase 2 trial of topical ruxolitinib for the treatment of patients with vitiligo.

Indication Status Update
Topical ruxolitinib (JAK1/JAK2) Atopic dermatitis, vitiligo Phase 2

Partnered
In July 2017, Lilly and Incyte announced that Japan’s Ministry of Health, Labor and Welfare granted marketing approval for Olumiant for the treatment of rheumatoid arthritis (including the prevention of structural injury of joints) in patients with inadequate response to standard-of-care therapies.

In July 2017, Lilly and Incyte announced that a resubmission to the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) for baricitinib will be delayed for a period anticipated to be a minimum of 18 months. The companies will be further discussing the path forward with the agency and evaluating options for resubmission, including the potential for an additional clinical study, as requested by the FDA.

Novartis has stated that it anticipates submitting an NDA for capmatinib, Incyte’s potent and selective c-MET inhibitor, in 2018.

Indication Status Update
Baricitinib (JAK1/JAK2)1 Rheumatoid arthritis Approved in Europe and Japan; CRL issued by FDA
Baricitinib (JAK1/JAK2)1 Psoriatic arthritis Lilly no longer expects Phase 3 to begin in 2017
Baricitinib (JAK1/JAK2)1 Atopic dermatitis, systemic lupus erythematosus Phase 2
Capmatinib (c-MET)2 Non-small cell lung cancer, liver cancer Phase 2 in EGFR wild-type ALK negative NSCLC patients with c-MET amplification and mutation

Notes:
1) Baricitinib licensed to Lilly
2) Capmatinib licensed to Novartis

Corporate Update
In June 2017, Lothar Finke, M.D. joined the Incyte Executive Management team as Head of Development Japan and General Manager, Japan. Dr. Finke was most recently the Head of Oncology Development and Medical Affairs Japan for Novartis where he was responsible for leading an integrated organization to support oncology development. He has significant experience developing drugs in all classes of oncology including immuno-oncology, targeted therapies and cell therapies in the EU, U.S., Canada, and Japan.

2017 Second-Quarter Financial Results
Revenues For the quarter ended June 30, 2017, net product revenues of Jakafi were $276 million as compared to $208 million for the same period in 2016, representing 33 percent growth. For the six months ended June 30, 2017, net product revenues of Jakafi were $527 million as compared to $391 million for the same period in 2016, representing 35 percent growth. For the quarter ended June 30, 2017, net product revenues of Iclusig were $16 million as compared to $4 million for the same period in 2016. For the six months ended June 30, 2017, net product revenues of Iclusig were $29 million as compared to $4 million for the same period in 20161.

For the quarter and six months ended June 30, 2017, product royalties from sales of Jakavi, which has been out-licensed to Novartis outside of the United States, were $34 million and $63 million, respectively, as compared to $26 million and $48 million for the same periods in 2016. For the quarter and six months ended June 30, 2017, product royalties from sales of Olumiant outside of the United States received from Lilly were $1 million.

For the quarter and six months ended June 30, 2017, contract revenues were $0 million and $90 million, respectively, as compared to $8 million and $66 million for the same periods in 2016. These contract revenues relate to milestone payments earned.

For the quarter ended June 30, 2017, total revenues were $326 million as compared to $246 million for the same period in 2016. For the six months ended June 30, 2017, total revenues were $711 million as compared to $510 million for the same period in 2016.

Year Over Year Revenue Growth
(in thousands, unaudited)

Three Months Ended Six Months Ended
June 30, % June 30, %
2017 2016 Change 2017 2016 Change
Revenues:
Jakafi net product revenue $ 276,038 $ 208,126 33% $ 527,115 $ 391,393 35%
Iclusig net product revenue 15,629 3,990 - 29,359 3,990 -
Product royalty revenues 34,769 25,958 34% 63,990 47,860 34%
Contract revenues - 8,214 - 90,000 66,429 -
Other revenues 8 - - 62 80 -
Total revenues $ 326,444 $ 246,288 33% $ 710,526 $ 509,752 39%

Research and development expenses Research and development expenses for the quarter and six months ended June 30, 2017 were $202 million and $610 million, respectively, as compared to $120 million and $277 million for the same periods in 2016. Included in research and development expenses for the quarter and six months ended June 30, 2017 were non-cash expenses related to equity awards to our employees of $23 million and $44 million, respectively. The increase in research and development expenses was primarily due to the expansion of the Company’s clinical portfolio as well as upfront and milestone expenses of $209 million related to our collaboration and license agreements with Agenus, Calithera and Merus.

Selling, general and administrative expenses Selling, general and administrative expenses for the quarter and six months ended June 30, 2017 were $90 million and $177 million, respectively, as compared to $67 million and $131 million for the same periods in 2016. Included in selling, general and administrative expenses for the quarter and six months ended June 30, 2017 were non-cash expenses related to equity awards to our employees of $11 million and $20 million, respectively. Increased selling, general and administrative expenses were driven primarily by additional costs related to the commercialization of Jakafi and the geographic expansion in Europe.

Change in fair value of acquisition-related contingent consideration The change in fair value of acquisition-related contingent consideration for the quarter and six months ended June 30, 2017 were $7 million and $14 million, respectively, as compared to $2 million for the same periods in 2016. The change in fair value of acquisition-related contingent consideration represents the fair market value adjustments of the Company’s contingent liability related to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.

Unrealized loss on long term investments Unrealized loss on long term investments for the quarter and six months ended June 30, 2017 were $20 million and $25 million, respectively, as compared to $1 million and $4 million for the same periods in 2016. The unrealized loss on long term investments for the quarter and six months ended June 30, 2017 represents the fair market value adjustments of the Company’s investments in Agenus and Merus.

Expense related to senior note conversions Expense related to senior note conversions for the quarter and six months ended June 30, 2017 were $1 million and $55 million, respectively, related to the conversions of certain of our 2018 and 2020 convertible senior notes.

Net income (loss) Net loss for the quarter ended June 30, 2017 was $12 million, or $0.06 per basic and diluted share, as compared to net income of $34 million, or $0.18 per basic and diluted share for the same period in 2016. Net loss for the six months ended June 30, 2017 was $200 million, or $1.00 per basic and diluted share, as compared to net income of $58 million, or $0.31 per basic and $0.30 per diluted share for the same period in 2016.
Cash, cash equivalents and marketable securities position As of June 30, 2017, cash, cash equivalents and marketable securities totaled $609 million as compared to $809 million as of December 31, 2016.
2017 Financial Guidance
The Company has updated its full year 2017 financial guidance, as detailed below.

Current Previous
Jakafi net product revenues $1,090-$1,120 million $1,020-$1,070 million
Iclusig net product revenues $60-$65 million Unchanged
Research and development expenses* $1,050-$1,150 million $1,000-$1,100 million
Selling, general and administrative expenses $340-$360 million Unchanged
Change in fair value of acquisition-related contingent consideration $30-$35 million Unchanged
* Includes upfront and milestone expenses of $209 million related to the amended Agenus collaboration, and the Merus and Calithera collaborations

About Jakafi (ruxolitinib)
Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea. Jakafi is also indicated for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.
Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States.

About Iclusig (ponatinib) tablets
Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

Incyte has an exclusive license from ARIAD Pharmaceuticals, Inc, since acquired by Takeda Pharmaceutical Company Limited, to develop and commercialize Iclusig in the European Union and 22 other countries, including Switzerland, Norway, Turkey, Israel and Russia.

On July 31, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported its financial results for the second quarter ended June 30, 2017, and provided an update on the Company’s recent activities (Press release, Ziopharm, JUL 31, 2017, View Source [SID1234519976]).

"ZIOPHARM is unique in the breadth and stage of technologies delivering cell- and gene-based therapies that are impactful, controllable and, most critically, scalable," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "We have seen ongoing validation of RheoSwitch gene switch technology through the now expanded Ad-RTS-hIL-12 + veledimex study in recurrent glioblastoma. We are addressing the complexities of commercializing CAR-T, T-cell receptor, and other cell-based therapies with our rapid manufacture of patient-derived T cells under point-of-care and our off-the-shelf natural killer cells. The Sleeping Beauty system enables us to generate CAR-T cells co-expressing important biological effectors such as membrane bound IL-15 and uniquely positions us to express TCRs to efficiently target multiple neoantigens in solid tumors. This non-viral approach to gene therapy not only allows us to customize immunotherapies, but enables controllable and cost-effective T cells with curative potential in both solid and hematologic malignancies."

"During the quarter, we presented updated data at ASCO (Free ASCO Whitepaper) that linked immune response to overall survival in patients with recurrent glioblastoma when treated with Ad-RTS-hIL-12 + veledimex. Additionally, we initiated a stereotactic arm in this study as a lead-in to both the pediatric and immune checkpoint combination trials. We continue to make progress toward finalizing a registration path for Ad-RTS-hIL-12 + veledimex while evaluating partnership opportunities for the program," added Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer of ZIOPHARM Oncology. "In our cell therapy programs, we continue to progress towards clinical evaluation of Sleeping Beauty engineered peripheral blood lymphocytes to express TCRs targeting solid tumors, we are advancing our non-viral point-of-care approach for CAR-T therapies, and we also anticipate the imminent initiation of the Phase 1 trial to evaluate CD33 as a new target for CAR+ T cells in patients with relapsed or refractory acute myeloid leukemia (AML), a highly aggressive and underserved disease. Additionally, we look forward to the initiation of a Phase 1 trial evaluating our off-the-shelf primary NK Cells, which have demonstrated the ability to eliminate AML in preclinical models."

Recent Updates

Adoptive Cell Therapies

ZIOPHARM is developing chimeric antigen receptor (CAR) T cell (CAR+ T), T-cell receptor (TCR) T cell (TCR+ T), and natural killer (NK) adoptive cell-based therapies. These programs are being advanced in collaboration with Intrexon Corporation (NYSE:XON) and selectively with MD Anderson Cancer Center, the National Cancer Institute (NCI) and/or Merck Serono, the biopharmaceutical business of Merck KGaA.

Announced FDA Acceptance of IND for CD33-Specific CAR-T Cell Therapy Targeting Relapsed/Refractory Acute Myeloid Leukemia. In May 2017, ZIOPHARM announced that an investigator-initiated Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for a Phase 1 trial infusing the Company’s CD33-specific CAR+ T cells for relapsed or refractory AML is active, with the first patient expected to begin treatment in the third quarter of 2017. The genetically modified T cells incorporate a kill switch to eliminate the infused product if there are serious adverse safety events.

Announced Advancement of Next-Generation Non-Viral CAR-T Cell Platform Empowered by Membrane-Bound IL-15 Under RTS Gene Switch Control. In April 2017, ZIOPHARM and its partners, Intrexon and Merck KGaA, Darmstadt, Germany, announced the advancement of a unique approach to develop therapeutic candidates for two CAR targets expressed on hematologic malignancies and solid tumors. The distinctive methodology centers on the proprietary RTS platform to regulate production of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty, a non-viral genetic modification system to genetically modify clinical-grade T cells. The companies expect to advance this innovative approach towards the clinic in 2018.

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The IL-15 cytokine is increasingly recognized as a key driver of therapeutic effect in CAR+ T therapy, including in a recent Journal of Clinical Oncology publication which correlated lymphoma remissions in patients whose IL-15 levels were elevated after lymphodepleting chemotherapy.i Through the RTS gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus potentiating a new paradigm in T-cell therapy.

Additionally, the non-viral Sleeping Beauty transposon-transposase system is an exceptional therapeutic tool that holds multiple advantages over viral-based delivery systems for stably introducing genes encoding CARs and TCRs into T cells. It simplifies genetic modification, and when coupled with reduced ex vivo processing, offers a pathway to shortened manufacturing and personalized T-cell therapies.

Continued to Advance Research under the Cooperative Research and Development Agreement with the National Cancer Institute Utilizing the Sleeping Beauty System to Generate TCR-modified T cells Targeting Neoantigens. ZIOPHARM continued to advance research being carried out under the Cooperative Research and Development Agreement (CRADA) that the Company maintains with the NCI. Announced in January 2017 by ZIOPHARM and partner Intrexon, research conducted under the CRADA will be carried out under the direction of Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI’s Center for Cancer Research. Dr. Rosenberg and his team are advancing the Sleeping Beauty system into clinical trials to target neoantigens in solid tumors on a patient-by-patient basis. These efforts are based on published works in which the Sleeping Beauty system is described as the most clinically advanced non-viral gene transfer tool to reprogram T cells for personalized immunotherapy.ii,iii

Ad-RTS-hIL-12 + veledimex

Ad-RTS-hIL-12 + veledimex is ZIOPHARM’s gene therapy candidate for the controlled expression of interleukin-12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using an RTS inducible gene switch that enables controlled in vivo expression of therapeutic proteins.

Announced Initiation of Stereotactic Treatment Cohort in Phase 1 Study of Ad-RTS-hIL-12 + Veledimex in Recurrent Glioblastoma. In June 2017, ZIOPHARM announced the initiation of enrollment in the stereotactic arm of its Phase 1 multicenter study of Ad-RTS-hIL-12 + veledimex, a gene therapy for controlled expression of IL-12, in patients with recurrent glioblastoma multiforme (rGBM). The stereotactic cohort will include rGBM patients, that are not scheduled to undergo surgical resection, to assess the safety and tolerability of a single dose of Ad-RTS-hIL-12 administered via injection and activated with orally-administered veledimex (20 mg QD, days 1-14). Stereotactic treatment will serve as a lead-in to the Company’s next phase of development for Ad-RTS-hIL-12 + veledimex in brain tumors, including planned anti‑PD‑1 combination therapy and pediatric studies.

Announced Positive Updated Results of Ad-RTS-hIL-12 + Veledimex in Recurrent Glioblastoma at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. In June 2017, ZIOPHARM announced updated results from its Phase 1 multicenter study of Ad-RTS-hIL-12 + veledimex, including the 20 mg expansion cohort in patients with recurrent or progressive GBM at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting June 2-6 in Chicago. As of May 24, 2017, the median overall survival of all patients receiving intratumoral Ad-RTS-hIL-12 with 20 mg of orally-administered veledimex was 12.5 months, with a mean follow-up time of 9.2 months. The majority of the 15 patients in the 20 mg cohort had two or more recurrences prior to entry in the study, indicating very advanced disease.

Based on the increased ratio of CD8+/FOXP3+ (effector/suppressor) T cells measured in peripheral blood 14 to 28 days after viral injection, overall survival appears correlated with IL-12-mediated cellular immune activation. Furthermore, patients who received low dose or no steroids showed a much better survival rate than those who received elevated systemic steroids, as the latter presumably interferes with immune activation.

As previously reported, a strong, dose-dependent correlation between veledimex dose, veledimex blood-brain-barrier penetration, and IL-12 and IFN-gamma production was observed. Drug-related toxicities, which were primarily non-neurologic, showed a dose response to veledimex, were consistent with those previously reported, and importantly, continue to be reversed upon cessation of the activator ligand, with no drug-related deaths.

Anticipated and Achieved 2017 Milestones

Intra-tumoral IL-12 RheoSwitch programs:
– Updated clinical data from Phase 1 of Ad-RTS-hIL-12 + veledimex for rGBM presented at ASCO (Free ASCO Whitepaper)
– Initiate pivotal clinical trial for rGBM
– Initiate stereotactic administration of Ad-RTS-hIL-12 + veledimex for rGBM:
– Initiate combination study of Ad-RTS-hIL-12 + veledimex with anti-PD-1 for rGBM
– Initiate Phase 1 study in the treatment of brain tumors in children
– Update program at the Society of Neuro-Oncology Annual Meeting
CAR+ T programs:
– Continue CD19-specific CAR+ T 2nd-generation clinical study, enrolling patients under shortened manufacturing protocol
– Advance mbIL15 CD19-specific CAR+ T 3rd generation toward a Phase 1 clinical study evaluating point-of-care
– Initiate a CD33-specific CAR+ T clinical study in adults and children for relapsed or refractory AML
– Advance CAR+ T preclinical studies for at least one hematological malignancy under a shortened manufacturing process towards point-of-care
TCR programs
– Execute CRADA with NCI utilizing Sleeping Beauty to generate T cells targeting neoantigens for treatment of patients with solid tumor malignancies
– Advance development of process for delivering personalized gene-modified T-cell products against neoantigens
NK cell programs
– Initiate a Phase 1 study of off-the-shelf NK cells for elderly patients with AML not eligible for standard intensive chemotherapy
GvHD programs
– Advance preclinical studies
Second-Quarter 2017 Financial Results

Net loss applicable to the common shareholders for the second quarter of 2017 was $17.7 million, or $(0.13) per share, compared to a net loss of $131.2 million, or $(1.01) per share, for the second quarter of 2016. The decrease is primarily due to the commitment to issue Series 1 preferred stock at fair value under the 2016 ECP Amendment and 2016 GvHD Amendment with Intrexon resulting in a $119.1 million non-cash charge during the three months ended June 30, 2016 that was not incurred during the three months ended June 30, 2017.
Research and development expenses were $10.8 million for the second quarter of 2017, compared to $129.2 million for the second quarter of 2016. The decrease in research and development expenses for the three months ended June 30, 2017 is primarily due to the Series 1 preferred stock issuance previously noted.
General and administrative expenses were $3.8 million for the second quarter of 2017, compared to $3.7 million for the second quarter of 2016.
The Company ended the quarter with unrestricted cash resources of approximately $97.2 million, plus approximately $27.3M in cash on hand at MD Anderson Cancer Center for programs to be conducted at MD Anderson Cancer Center under the current Research and Development Agreement. The Company believes its current resources will be sufficient to fund its currently planned operations into the fourth quarter of 2018.

On July 31, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that NERLYNX (neratinib) tablets, formerly known as PB272, is now commercially available by prescription in the United States (Press release, Puma Biotechnology, JUL 31, 2017, View Source [SID1234519956]). The U.S. Food and Drug Administration (FDA) approved NERLYNX on July 17, 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy.

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FDA approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of NERLYNX following adjuvant trastuzumab treatment. Women (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either NERLYNX (n=1,420) or placebo (n=1,420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in patients treated with NERLYNX compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008).

The most common adverse reactions (≥5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of NERLYNX-treated patients. Increases in liver transaminases led to drug discontinuation in 1.7% of NERLYNX-treated patients.

"Like many women with breast cancer, those with HER2-positive disease often struggle with anxiety and fear of recurrence," said Jennifer Merschdorf, Chief Executive Officer of Young Survival Coalition. "We are always eager for treatment advances that may provide an opportunity to further reduce the risk of recurrence."

"Despite advances in the treatment of early stage HER2-positive breast cancer, there remains a need for further therapeutic improvements in order to attempt to further reduce the risk of disease recurrence," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to be able to bring this new medicine to patients with breast cancer. We would like to express our appreciation to the patients, caregivers and physicians who contributed to the NERLYNX clinical development program and, more specifically, the ExteNET trial."

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

The full prescribing information for NERLYNX is available at www.NERLYNX.com. The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

A Marketing Authorisation Application for neratinib is under review by the European Medicines Agency (EMA).

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Indication

NERLYNX is a tyrosine kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Important Safety Information

There are possible side effects of NERLYNX. Patients must contact their doctor right away if they experience any of these symptoms. NERLYNX treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects.

Diarrhea

Diarrhea is a common side effect of NERLYNX. The diarrhea may be severe, and you may get dehydrated. Your healthcare provider should prescribe the medicine loperamide for you during your first 2 cycles (56 days) of NERLYNX and then as needed. To help prevent or reduce diarrhea:

You should start taking loperamide with your first dose of NERLYNX.
Keep taking loperamide during the first 2 cycles (56 days) of NERLYNX treatment and then as needed. Your healthcare provider will tell you exactly how much and how often to take loperamide.
While taking loperamide, you and your healthcare provider should try to keep the number of bowel movements that you have at 1 or 2 bowel movements each day.
Tell your healthcare provider if you have more than 2 bowel movements in 1 day, or if you have diarrhea that does not go away.
Contact your healthcare provider right away if you have severe diarrhea or if you have diarrhea along with weakness, dizziness, or fever.

Liver Problems

Changes in liver function tests are common with NERLYNX. The patient’s doctor will do tests before starting treatment, monthly during the first 3 months, and then every 3 months as needed during treatment with NERLYNX. NERLYNX treatment may be stopped or the dose may be lowered if your liver tests show severe problems. Symptoms of liver problems may include tiredness, nausea, vomiting, pain in the right upper stomach area (abdomen), fever, rash, itching, yellowing of your skin or whites of your eyes.

Pregnancy

Patients should tell their doctor if they are planning to become pregnant, are pregnant, plan to breastfeed, or are breastfeeding. NERLYNX can harm your unborn baby. Birth control should be used while a patient is receiving NERLYNX and for at least 1 month after the last dose. If patients are exposed to NERLYNX during pregnancy, they must contact their healthcare provider right away.

Common side effects in patients treated with NERLYNX

In clinical studies, the most common side effects seen in patients taking NERLYNX were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis (dry or inflamed mouth, or mouth sores), decreased appetite, muscle spasms, dyspepsia, changes in liver blood tests results, nail problems, dry skin, abdominal distention, weight loss, and urinary tract infection.

Patients should tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or View Source . Patients and caregivers may also report side effects to Puma Biotechnology at 1-844-NERLYNX (1-844-637-5969).

Please see Full Prescribing Information, available at www.NERLYNX.com .

On July 31, 2017 Geron Corporation (Nasdaq:GERN) reported updates to the clinical development plans for IMerge and IMbark, the ongoing trials of the telomerase inhibitor imetelstat in lower risk myelodysplastic syndromes (MDS) and relapsed or refractory myelofibrosis (MF), respectively, being conducted by Janssen Research & Development, LLC (Press release, Geron, JUL 31, 2017, View Source [SID1234519955]). For IMerge, Part 1 will be expanded to enroll additional patients in a refined MDS population to confirm the clinical benefit and safety observed from current results. For IMbark, the trial remains unchanged. Geron expects that the IMbark protocol-specified primary analysis, the completion of which triggers a future Continuation Decision by Janssen, will begin no later than the third quarter of 2018.

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Original Trial Design

IMerge (NCT02598661) is a Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The clinical trial is in two parts: Part 1 is a Phase 2, open-label, single-arm design in approximately 30 patients and Part 2 is designed to be a Phase 3, randomized, controlled trial in approximately 170 patients. The primary efficacy endpoint is the rate of red blood cell (RBC) transfusion independence (TI) lasting at least 8 weeks.

Trial Status Update

In Part 1 of IMerge, 32 patients were enrolled, of which a subset of 13 patients had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a del(5q) chromosomal abnormality. As of May 2017, the 13-patient subset showed an increased durability and rate of transfusion independence compared to the overall trial population (≥8-week RBC-TI: 53.8% vs 34.4%). The safety profile in Part 1 was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. The most common adverse events were cytopenias, which were manageable, and included grade 3/4 neutropenia and thrombocytopenia.

Based on these data from the 13-patient subset, the Joint Steering Committee has decided to amend Part 1 of the protocol to enroll approximately 20 additional patients who are non-del5q and naïve to HMA and lenalidomide treatment in order to increase the experience and confirm the benefit-risk profile of imetelstat dosed at 7.5 mg/kg every four weeks in this refined target patient population. Enrollment into the expanded Part 1 is expected to begin in the fourth quarter of 2017.

Separately, a data package and proposed refinements to the trial design for Part 2 of IMerge were previously provided to the FDA following an internal data review completed by Janssen in April, and related interactions are ongoing. Feedback from ongoing FDA interactions, data from the expanded Part 1, and other imetelstat program information, including the protocol-specified primary analysis for IMbark, are expected to inform Janssen’s decision of whether to move forward to Part 2 of IMerge.

Detailed results for the original 32 patients in Part 1 of IMerge, including key secondary endpoints of hematologic improvement and rate of RBC-TI lasting at least 24 weeks, as well as duration of response and detailed safety information, will be submitted for presentation at a major medical conference.

IMbark

Trial Status Update

IMbark (NCT02426086) is a Phase 2 trial in patients with Intermediate-2 or High Risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The trial continues without modification, and patients remaining in the treatment phase may continue to receive imetelstat. All safety and efficacy assessments will be conducted as planned in the protocol, which includes an assessment of a potential survival benefit associated with imetelstat treatment. To date, median overall survival has not yet been reached in either the 4.7 mg/kg or 9.4 mg/kg dosing arm. Enrollment of new patients to the trial remains suspended because the total number of patients enrolled to date is adequate to perform the protocol-specified primary analysis. Geron expects Janssen to perform an internal data review in the first quarter of 2018 to enable a potential protocol amendment to allow the long-term treatment and follow-up of patients, including for survival, beyond the current April 2018 per-protocol end-of-study date.

Continuation Decision

The Joint Steering Committee has agreed that the timing of the protocol-specified primary analysis for IMbark will begin upon the earlier of either a pre-specified number of deaths occurring in the trial or the end of the third quarter of 2018. Following completion of this primary analysis, which includes an assessment of potential survival benefit associated with imetelstat treatment, Janssen will notify Geron whether it elects to maintain the license rights and continue the development of imetelstat in any indication, i.e., the Continuation Decision.

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms and cytopenias. Imetelstat has not been approved for marketing by any regulatory authority.