On May 9, 2017 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported its first quarter 2017 financial results and provided an update on the company, including its progress with IPI-549, a potentially first-in-class immuno-oncology product candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma) (Press release, Infinity Pharmaceuticals, MAY 9, 2017, View Source [SID1234518964]).

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Infinity is evaluating IPI-549 as a monotherapy and in combination with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, in a Phase 1 study in patients with advanced solid tumors. Dose-escalation data from the ongoing study were presented in April at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington, D.C. These data demonstrated that IPI-549 was well tolerated both as a monotherapy and in combination with Opdivo. Additionally, data from the monotherapy module of the study showed IPI-549 has a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile that supports once daily (QD) dosing. IPI-549 is believed to be the only selective PI3K-gamma inhibitor in clinical development.

"IPI-549 has a number of key attributes that have enabled us to rapidly enroll patients in our ongoing study. It is orally administered, is believed to be the only selective PI3K-gamma inhibitor in clinical development, and has demonstrated a favorable tolerability profile, both as a monotherapy as well as in combination with Opdivo," stated Adelene Perkins, Infinity’s chair and chief executive officer. "Additionally, there is a strong body of preclinical translational research supporting the program demonstrating that selectively targeting PI3K-gamma with IPI-549 reprograms macrophages from a pro-tumor to an anti-tumor phenotype and is able to help overcome resistance to checkpoint inhibition, representing a unique and potentially transformative approach within immuno-oncology."

"Our dose-escalation phases evaluating IPI-549 alone and with Opdivo are ongoing, and we are on track to initiate the expansion phases in the second half of the year. The expansion phases will allow us to generate additional clinical data from monotherapy treatment as well as from the combination of IPI-549 and Opdivo in specific types of solid tumors. We are pleased with the data we recently presented at the AACR (Free AACR Whitepaper) Annual Meeting 2017, and we expect to report additional data from this study in the second half of the year," continued Ms. Perkins.

The ongoing Phase 1 study is designed to evaluate the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in approximately 175 patients with advanced solid tumors. The study includes four phases, or modules: monotherapy dose escalation, combination therapy dose escalation, monotherapy expansion, and combination therapy expansion. The combination expansion module will include multiple cohorts designed to evaluate IPI-549 in patients with specific types of cancer, including patients with non-small cell lung cancer (NSCLC), melanoma, and squamous cell carcinoma of the head and neck (SCCHN) whose tumors show initial resistance or subsequently develop resistance to immune checkpoint blockade therapy. There is a great need for additional treatment options for the growing number of patients living with these cancers, which account for more than 17 percent of all new cancer cases in the U.S.1,2

Recent Developments

Dose-escalation modules of Phase 1 study of IPI-549 ongoing: Infinity reported today that it has completed an analysis of a cohort of patients who received IPI-549 40 mg QD and has begun enrolling patients in a cohort to evaluate IPI-549 60 mg QD. The company expects to complete the monotherapy dose-escalation module in the first half of the year and subsequently initiate patient enrollment in the monotherapy expansion module in the second half of 2017.

Infinity also reported today that it is continuing to evaluate data from the dose-escalation cohort evaluating IPI-549 30 mg QD in combination with Opdivo. The company expects to complete the combination dose-escalation module and initiate the combination expansion module in the second half of 2017.

Updated Phase 1 clinical data presented at AACR (Free AACR Whitepaper) Annual Meeting 2017: New Phase 1 data from a March 20, 2017, data cutoff were presented during a poster session at the AACR (Free AACR Whitepaper) Annual Meeting 2017. The presentation included data from 15 evaluable patients who received monotherapy doses of IPI-549 ranging from 10 mg to 40 mg QD and six evaluable patients who received IPI-549 20 mg QD in combination with Opdivo.

Data from the monotherapy dose-escalation module demonstrated that IPI-549 treatment was well tolerated. Among the 15 evaluable patients, no dose limiting toxicities or serious drug-related side effects occurred, and no side effects led to treatment discontinuation or dose reduction. The PK and PD properties of IPI-549 appeared favorable, with near-complete and sustained inhibition of PI3K-gamma at doses at or above 20 mg QD, supporting once daily dosing of IPI-549.

Preliminary data from the combination dose-escalation module evaluating 20 mg IPI-549 in combination with Opdivo demonstrated that the treatment regimen was well tolerated and did not result in new or unexpected side effects relative to the known safety profile of each treatment when administered as monotherapy. Among the six evaluable patients, no dose limiting toxicities or serious drug-related side effects occurred, and no side effects led to treatment discontinuation. The PK profile of IPI-549 in combination with Opdivo appeared favorable and suggested that Opdivo does not affect the PK properties of IPI-549.

Rationale for targeting PI3K-gamma and preclinical data for IPI-549 presented at AACR (Free AACR Whitepaper) Annual Meeting 2017: Jeffery Kutok, M.D., Ph.D., Infinity’s chief scientific officer, presented the rationale for targeting PI3K-gamma during an educational session at the AACR (Free AACR Whitepaper) Annual Meeting 2017. In contrast to the other three major PI3K isoforms, PI3K-gamma is highly expressed in tumor-associated macrophages and plays an important role in the pro-tumor function of these cells. Infinity’s scientists designed IPI-549 to be not only a very potent but also a highly selective PI3K-gamma inhibitor, and it has greater than 100-fold selectivity for PI3K-gamma over the other major PI3K isoforms.

During the educational session, Dr. Kutok also summarized the preclinical rationale for targeting PI3K-gamma previously reported in two publications in Nature.3,4 Preclinical research has demonstrated that blockade of PI3K-gamma signaling by treatment with IPI-549 results in a transcriptional reprogramming of macrophages. This reprogramming shifted macrophages in the tumor microenvironment from the M2, or pro-tumor phenotype, to the M1, or anti-tumor phenotype, increased the number and activity of anti-tumor T cells that attack the tumor and also increased the production of pro-inflammatory cytokines.

Preclinical data from multiple solid tumor models demonstrated that IPI-549 was active as a monotherapy and that IPI-549 administered in combination with checkpoint inhibition led to enhanced activity compared to either treatment alone. Additionally, preclinical data demonstrated that M2, pro-tumor macrophages are associated with resistance to checkpoint inhibitor monotherapy and that treatment with IPI-549 in combination with checkpoint inhibitors is able to overcome this resistance by reprogramming macrophages from the M2, pro-tumor phenotype to the M1, anti-tumor phenotype. Taken together, these preclinical data demonstrate that PI3K-gamma plays a key role in the immuno-suppressive tumor microenvironment, help to further elucidate the mechanism of action for IPI-549 and provide a strong rationale for the ongoing Phase 1 study of IPI-549.
First Quarter 2017 Financial Results

At March 31, 2017, Infinity had total cash, cash equivalents and available-for-sale securities of $75.4 million, compared to $92.1 million at December 31, 2016. Cash used for operating activities during the first quarter of 2017 included $5.2 million of payments related to the company’s 2016 restructuring activities.
Infinity did not record any revenue during the first quarter of 2017. Revenue for the first quarter of 2016 was $9.3 million, all of which related to Infinity’s previous collaboration agreement with AbbVie Inc.
Research and development (R&D) expense for the first quarter of 2017 was $4.0 million, compared to $39.2 million for the same period in 2016. The decrease in R&D expense was primarily related to a decrease in clinical development expenses for duvelisib in addition to the company’s 2016 restructuring activities.
General and administrative (G&A) expense was $6.4 million for the first quarter of 2017 compared to $10.8 million for the same period in 2016. The decrease in G&A expense was primarily due to the company’s 2016 restructuring activities.
Net loss for the first quarter of 2017 was $10.5 million, or a basic and diluted loss per common share of $0.21, compared to a net loss of $40.7 million, or a basic and diluted loss per common share of $0.82, for the first quarter of 2016.
Cash and Investments Outlook
Infinity’s 2017 financial outlook remains as follows:

Net loss: Infinity expects net loss for 2017 to range from $40 million to $50 million.
Cash and Investments: Infinity expects to end 2017 with a cash, cash equivalents and available-for-sale securities balance ranging from $40 million to $50 million.
Based on its current operational plans, Infinity expects that its existing cash, cash equivalents and available-for-sale securities at March 31, 2017, will be adequate to satisfy the company’s capital needs into the first quarter of 2019. The company’s financial outlook excludes additional funding or business development activities.

About the IPI-549 and the Ongoing Phase 1 Study
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 reprograms macrophages from a pro-tumor to an anti-tumor phenotype and is able to overcome resistance to checkpoint inhibition.3,4 As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors.5 The study includes monotherapy and combination dose-escalation phases, in addition to a monotherapy expansion cohort and combination expansion cohorts. The expansion cohorts evaluating IPI-549 plus Opdivo will include patients with non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN). Patients enrolled in these combination expansion cohorts represent a difficult-to-treat population, as they must have demonstrated initial resistance or subsequently develop resistance to a PD-1 or PD-L1 therapy immediately prior to enrolling in the study. Overall, the study is expected to enroll approximately 175 patients.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On May 9, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported financial results and recent highlights for the first quarter ended March 31, 2017 (Press release, Halozyme, MAY 9, 2017, View Source [SID1234518963]).

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"The first quarter was marked by strong progress in our ongoing clinical studies of PEGPH20 and continued momentum with partners of our ENHANZE technology," said Dr. Helen Torley, president and chief executive officer. "Enrollment is progressing to plan in HALO-301, our ongoing Phase 3 study of PEGPH20 in pancreas cancer patients and in the HALO-101 study of PEGPH20 in combination with KEYTRUDA in advanced gastric and non-small cell lung cancer patients, supporting the potential for first efficacy data in combination with a PD-1 inhibitor in the fourth quarter. In addition, we are delighted that our Phase 2 HALO-202 study was selected for an oral presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.

"At the same time, the outlook for our ENHANZE technology has never been stronger following the unanimous FDA advisory committee in March supporting rituximab SC. Our pipeline of active partner discussions has continued to expand, and while the timing for new ENHANZE collaboration agreements is unpredictable, it remains our goal to sign another agreement in 2017."

First Quarter 2017 and Recent Highlights include:

Acceptance of Halozyme’s Phase 2 randomized HALO-202 study data for an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting. The presentation will expand on the topline results shared in January with additional data from the study as of December 2016.

Enrollment tracking to plan in HALO-301, the company’s Phase 3 study of pancreas cancer patients at over 200 global sites in 22 countries.

Progressing in the dose expansion phase of the ongoing Phase 1b clinical study evaluating PEGPH20 in combination with KEYTRUDA (pembrolizumab) in relapsed non-small cell lung and gastric cancer patients. Enrollment is progressing to plan and may enable Halozyme to report response rate data by the end of the year, depending on the pace of enrollment and time to response.

Presenting data showing PEGPH20 increases immune response and effectiveness of immunotherapies in preclinical animal models at the American Association of Cancer Research annual meeting. The research showed a significant increase in the accumulation of cancer-fighting CD8+ T cells in mice treated with PEGPH20, and that PEGPH20 increased the effectiveness of an anti-PD-L1 therapy by 411 percent compared to anti-PD-L1 alone as measured by tumor growth inhibition in an HA-rich mouse model.

Announcing an Oncologic Drug Advisory Committee of the U.S. Food and Drug Administration voted 11 to 0 that the benefit/risk of rituximab/hyaluronidase for subcutaneous injection was favorable for patients in the proposed indications of follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia. The FDA action date is June 26. Analysts estimate rituxumab sales in oncology indications in the United States were approximately $3 billion in 2016.

Advancing the development of multiple products using Halozyme’s ENHANZE technology. Roche continues in its ongoing Phase 1 study to examine the combination of Herceptin SC and a subcutaneous formulation of Perjeta using ENHANZE, including investigation into whether a single injection of the combination can be achieved, potentially providing a significant convenience for patients.

In addition, Janssen has developed a rapid delivery SC formulation of daratumumab using ENHANZE technology and recently dosed the first patients as part of their ongoing Phase 1 study. Janssen is currently planning to initiate a Phase 3 study using the new formulation later this year.

The collaboration with Lilly using Halozyme’s ENHANZE technology is progressing across multiple targets with preclinical and clinical studies this year and next.
First Quarter 2017 Financial Highlights

Revenue for the first quarter was $29.6 million compared to $42.5 million for the first quarter of 2016. The year-over-year decrease was driven by $15.5 million received in license and milestone payments from Lilly, AbbVie and Pfizer in the first quarter of 2016, partially offset by increases in royalties from partner sales of Herceptin SC, MabThera SC and HYQVIA, and research and development reimbursements from ENHANZE partners. Revenue for the first quarter included $14 million in royalties, an increase of 23 percent from the prior-year period, $8.2 million in sales of bulk rHuPH20 primarily for use in manufacturing collaboration products and $3.2 million in HYLENEX recombinant (hyaluronidase human injection) product sales.

Research and development expenses for the first quarter were $36.9 million, compared to $40.1 million for the first quarter of 2016. The decrease was driven by drug product purchases for the HALO-301 study as well as one-time costs related to companion diagnostic development.
Selling, general and administrative expenses for the first quarter were $12.6 million, compared to $10.8 million for the first quarter of 2016. The increase was primarily due to personnel expenses, including stock compensation, for the
period.

Net loss for the first quarter was $32.9 million, or $0.26 per share, compared to net loss in the first quarter of 2016 of $19.8 million, or $0.16 per share.
Cash, cash equivalents and marketable securities were $179 million at March 31, 2017, compared to $205 million at December 31, 2016.
Financial Outlook for 2017

For 2017, the company reiterated its financial guidance of:

Net revenue of $115 million to $130 million;
Operating expenses of $240 million to $250 million;
Operating cash burn of $75 million to $85 million; and
Year-end cash balance of $110 million to $125 million.

On May 9, 2017 Geron Corporation (Nasdaq:GERN) reported financial results for the first quarter ended March 31, 2017 and recent events (Press release, Geron, MAY 9, 2017, View Source [SID1234518962]).

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First Quarter 2017 Results

For the first quarter of 2017, the company reported operating revenues of $537,000 and operating expenses of $8.0 million compared to $749,000 and $9.8 million, respectively, for the comparable 2016 period. Revenues for the first quarter of 2017 and 2016 included royalty and license fee revenues under various non-imetelstat license agreements. Net loss for the first quarter of 2017 was $7.2 million, or $0.05 per share, compared to $8.8 million, or $0.06 per share, for the comparable 2016 period. The company ended the first quarter of 2017 with $121.7 million in cash and investments.

Research and development expenses for the three months ended March 31, 2017 and 2016 were $3.4 million and $5.0 million, respectively, and largely reflect the company’s proportionate share of clinical development expenses under the imetelstat collaboration with Janssen Biotech, Inc. (Janssen). Higher research and development expenses in 2016 were primarily due to start-up costs for the initiation of IMerge, the Phase 2/3 trial in myelodysplastic syndromes being conducted by Janssen, in which the first patient was dosed in January 2016.

General and administrative expenses for the three months ended March 31, 2017 and 2016 were $4.7 million and $4.8 million, respectively. The decrease in general and administrative expenses in 2017 compared to 2016 primarily reflects reduced consulting costs.

Interest and other income for the three months ended March 31, 2017 and 2016 were $332,000 and $256,000, respectively. The increase in interest and other income in 2017 compared to 2016 primarily reflects higher yields on the company’s marketable securities portfolio.

"As a result of the second internal data reviews that were completed in April for the imetelstat clinical trials in myelodysplastic syndromes and myelofibrosis, both trials are continuing unmodified. For IMerge, the next step is a decision regarding the Phase 3 portion of the trial. If Janssen decides to move forward, we expect the Phase 3 portion to be open to patient enrollment in the fourth quarter. For IMbark, we expect Janssen to evaluate maturing data from the trial during the next year, including an assessment of overall survival," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We continue to be pleased by the commitment to imetelstat shown by our colleagues at Janssen. Their conduct of these internal data reviews has highlighted to us the care and professional development expertise they are applying to this innovative drug."

Recent Company Events

Imetelstat Clinical Development

The telomerase inhibitor imetelstat is being evaluated in two ongoing clinical trials, IMerge and IMbark, as conducted by Janssen under the terms of an exclusive worldwide license and collaboration agreement. IMerge is a Phase 2/3 clinical trial designed to evaluate imetelstat in transfusion dependent patients with IPSS low or intermediate-1 risk myelodysplastic syndromes (MDS) who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). IMbark is a Phase 2 clinical trial designed to evaluate two dose levels of imetelstat in patients with intermediate-2 or high risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a JAK inhibitor.

In April 2017, the second internal data reviews of IMerge and IMbark were completed. Based on these reviews, the Joint Steering Committee determined the following:

Both trials continue unmodified, and patients remaining in the treatment phases may continue to receive imetelstat.

The safety profile of imetelstat in both trials was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified.

For IMerge, the benefit/risk profile of imetelstat in the Phase 2 patients supports continued development in lower risk MDS. A data package and proposed design refinements to the Phase 3 component of the trial are planned to be provided to the FDA. In addition, the Phase 2 data from IMerge are expected to be submitted for consideration for presentation at a medical conference in the future.

For IMbark, the current results suggest clinical benefit and a potential overall survival benefit associated with imetelstat treatment in relapsed or refractory MF. Enrollment of new patients to the trial remains suspended because the total number of patients enrolled to date is adequate to assess longer-term outcome measures, including overall survival, when the data are fully matured.
Geron expects further decisions by Janssen on the development of imetelstat will be informed by maturing efficacy and safety data from the trials, feedback from health authorities, and the totality of imetelstat program information, including an assessment of the evolving treatment landscapes in MDS and MF and the potential application of imetelstat in multiple hematologic malignancies.

Poster Presentation

Non-clinical data on imetelstat was presented as a poster by Janssen at the 2017 annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April:

Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia (Abstract #1101)

Data presented described non-clinical results of imetelstat’s activity in combination with venetoclax, a selective BCL-2 inhibitor. In acute myeloid leukemia (AML) cell lines, telomerase expression and activity were decreased by imetelstat and further reduced in combination with venetoclax. In addition, imetelstat enhanced apoptosis induced by venetoclax in AML cell lines and AML patient samples. Combining imetelstat with venetoclax in an AML mouse model prolonged survival, with four of ten mice alive approximately 80 days after treatment was stopped.
The poster is available on Geron’s website at www.geron.com/presentations.

On May 9, 2017 Portola Pharmaceuticals Inc. (Nasdaq:PTLA) reported that clinical results from the Phase 2 study of cerdulatinib in patients with relapsed/refractory b-cell malignancies will be shared in an oral presentation at the International Conference on Malignant Lymphoma (ICML), which is taking place from June 14-17 in Lugano, Switzerland (Press release, Portola Pharmaceuticals, MAY 9, 2017, View Source [SID1234518957]).

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Cerdulatinib is an investigational oral, dual SYK/JAK kinase inhibitor in development to treat patients with resistant or relapsed hematologic cancers. Cerdulatinib inhibits two key signaling pathways that promote cancer cell growth in certain hematologic malignancies.
Details regarding the oral presentation follow.

Oral Presentation Details:

Abstract Title: The Dual SYK/JAK Inhibitor Cerdulatinib Demonstrates Rapid Tumor Responses in a Phase 2 Study in Patients with Relapsed/Refractory B-Cell Malignancies
Presenting Author: P.A. Hamlin, Memorial Sloan Kettering Cancer Center
Presentation Date and Time: June 15, 2017 at 4:40 p.m. CEST
Location: Room A, Cinema Corso and Aula Magna (Lugano University)