On November 9, 2015 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported financial results for the third quarter ended September 30, 2015 (Press release, Halozyme, NOV 9, 2015, View Source [SID:1234508158]). Revenue for the quarter of $20.8 million and a net loss of $24.5 million, or $0.19 per share, compared to revenue of $14.6 million and a net loss of $20.3 million, or $0.16 per share, for the third quarter of 2014. Financial results for the quarter were in line with company expectations and its annual financial guidance, which the company reiterated today.

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"With more than 100 patients now enrolled in Stage 2 of our Phase 2 study in pancreatic cancer patients, we are on track to close enrollment by the end of the year and achieve a major milestone toward our goal of ultimately commercializing PEGPH20," said Dr. Helen Torley, president and CEO. "Strong progress was made towards our goal of evaluating the pan tumor potential of PEGH20 by dosing the first patient in our immuno-oncology clinical trial in combination with Merck’s KEYTRUDA and by executing well on our broader clinical trial roadmap, including planning for initiation of our Phase 3 study in pancreatic cancer at the end of the first quarter of 2016.

"At the same time, our ENHANZE technology platform continued to deliver a growing royalty revenue stream from collaboration and licensing agreements with Roche and Baxalta, and we achieved important milestones toward potential future royalties with Pfizer, Janssen and AbbVie. Further progress was demonstrated by Pfizer and Janssen who initiated dosing in separate Phase 1 clinical trials with ENHANZE, while AbbVie announced plans to work with Halozyme on HUMIRA (adalimumab) with the goal to help reduce the number of induction injections and deliver additional performance benefits."

Third Quarter 2015 Highlights and Subsequent Events include:

Enrolling more than 100 patients to date in Stage 2 of Halozyme Study 202 of investigational new drug PEGPH20 in metastatic pancreatic ductal adenocarcinoma patients. Halozyme plans to complete its target enrollment of 114 patients by the end of 2015 and present results of the study in the second half of 2016.

Submitting Study 301 protocol to the FDA and European Regulatory Authorities. This Phase 3 study of PEGPH20 in previously untreated metastatic pancreatic cancer patients is planned for initiation by the end of first quarter 2016. Halozyme also made progress during the quarter with its partner Ventana toward completing a companion diagnostic test that will be used to prospectively screen patients for high levels of hyaluronan (HA). HA is a glycosaminoglycan, or chain of natural sugars in the body that accumulate around certain tumors. PEGPH20 is designed to temporarily degrade HA, improving the access of co-administered therapies.

Dosing the first patient in Halozyme’s Phase 1b study of PEGPH20 plus KEYTRUDA (pembrolizumab). The company is studying patients with relapsed/refractory Stage IIIB/IV non-small cell lung cancer and recurrent locally advanced or metastatic gastric adenocarcinoma. This trial is Halozyme-sponsored and is being conducted at a number of leading oncology centers with KEYTRUDA experience.

Progressing into a second dosing cohort in the Halozyme Phase 1b/2 PRIMAL study of PEGPH20 plus docetaxel in non-small cell lung cancer patients. Actions initiated during the quarter have resulted in an increase in the number of patients screened for the study. Once a maximum tolerated dose is determined, the company plans to expand the study with additional sites outside the U.S. and screen patients prospectively for trial eligibility based on high levels of HA.

Advancing Halozyme’s clinical collaboration with Eisai toward initiation of its Phase 1b/2 study in the first quarter of 2016. Halozyme and Eisai will co-fund the clinical trial to explore whether HALAVEN (eribulin) in combination with PEGPH20 can improve overall response rate, as compared with HALAVEN alone as a therapy for advanced HER2-negative high-HA metastatic breast cancer patients.

Achieving partner clinical milestones with the Halozyme ENHANZE technology platform, including Pfizer’s first dosing of healthy subjects with rivipansel and ENHANZE in a Phase 1 clinical trial; Janssen’s first dosing of the anti-CD38 daratumumab with ENHANZE in a Phase 1b clinical trial in multiple myeloma patients; and AbbVie announcing plans for HUMIRA a (adalimumab) under a collaboration and licensing agreement formed with Halozyme in June of 2015, with a goal to help reduce the number of induction injections at higher doses and deliver additional performance benefits.

Third Quarter 2015 Financial Highlights

Revenue for the third quarter was $20.8 million, compared to $14.6 million for the third quarter of 2014, driven primarily by an increase in royalties from partner sales of Herceptin SC, MabThera SC and HyQvia. Revenue for the quarter included $8.3 million in royalties, $6.3 million in sales of bulk rHuPH20 for use in manufacturing collaboration products, $3.9 million in HYLENEX recombinant (hyaluronidase human injection) product sales, and $2.2 million in collaboration revenue.

Research and development expenses for the third quarter were $27.6 million, compared to $19.9 million for the third quarter of 2014. The planned increase was primarily due to expenses for preclinical and clinical support of PEGPH20.

Selling, general and administrative expenses for the third quarter were $10.2 million, compared to $8.6 million for the third quarter of 2014. The increase was primarily due to an increase in personnel expenses, including stock compensation, for the period.
Net loss for the third quarter was $24.5 million, or $0.19 per share, compared to a net loss in the third quarter of 2014 of $20.3 million, or $0.16 per share.

Cash, cash equivalents and marketable securities were $123.7 million at Sept. 30, compared to $140.7 million at June 30, 2015.

Financial Outlook

For the full year 2015, the company maintains its previously announced guidance of:

Net revenues to be in the range of $110 million to $115 million;
Operating expenses to be in the range of $160 million to $170 million; and
Net cash burn to be between $20 million to $30 million.

On November 9, 2015 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported its financial results for the third quarter ended September 30, 2015. As of September 30, 2015, cash, cash equivalents and investments totaled $81.9 million (Filing, 8-K, Calithera Biosciences, NOV 9, 2015, View Source [SID:1234508336]).

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"In the third quarter, we continued to move clinical programs forward with presentations of data at key medical meetings," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We presented dose expansion monotherapy cohorts for our lead product CB-839 at the AACR (Free AACR Whitepaper)-EORTC-NCI meeting, and we are currently opening enrollment across six combination cohorts. For our lead immuno-oncology program, we presented initial preclinical data for CB-1158, an oral, small molecule arginase inhibitor with the potential to treat cancer by blocking the immunosuppression of the tumor micro-environment. We believe that we have multiple opportunities to positively impact clinical outcomes for cancer patients by building a pipeline of novel therapeutic product candidates."

Third Quarter 2015 and Recent Highlights

• CB-839 Solid Tumor Phase 1 data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting. On November 8, 2015, solid tumor phase 1 data were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper)-National Cancer Institute (NCI)-European Organization for Research and Treatment of Cancer (EORTC) meeting that demonstrated the clinical activity, tolerability and unique mechanism of action of CB-839 as a single agent in patients with solid tumors. Among efficacy-evaluable patients across a range of tumor types treated on the twice daily schedule of CB-839 administered with food, 22 of 50 patients (44%) had stable disease (SD) or better lasting at least 3 cycles (63 days). One renal cell carcinoma (RCC) patient has an ongoing partial response (PR; on study > 5 months); this patient showed a 32% reduction in target lesions by RECIST with generalized shrinkage of lymph node metastases. Among the 15 evaluable patients with RCC, 9 (60%) had SD or PR, with four patients remaining on study.

• Arginase inhibitor CB-1158 preclinical data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC Meeting. Calithera selected CB-1158 as the clinical candidate for Calithera’s first immuno-oncology program targeting inhibition of arginase, a critical T-Cell immunosuppressive enzyme produced by myeloid-derived suppressor cells in tumors. On November 6, 2015, Calithera presented data at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting showing that CB-1158 is a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency. Administration of CB-1158 to mice results in a dose-dependent increase in tumor arginine levels, consistent with target inhibition. Evaluation of anti-tumor efficacy in immunocompetent syngeneic mouse models has shown that oral administration of CB-1158 results in significant inhibition of tumor growth, and it combines well with checkpoint inhibitors with no evidence of additional toxicity.

• Augmented Board of Directors. In September 2015, Calithera appointed Sunil Agarwal, M.D., Senior Vice President and Chief Medical Officer at Ultragenyx, to the company’s Board of Directors.
Anticipated Upcoming Milestones

• Hematologic Phase 1 clinical trial data by year end 2015

• Initiation of six CB-839 combination expansion cohorts by year end 2015

• CB-839 combination therapy data in mid-2016

• Filing of investigational new drug application (IND) for arginase inhibitor CB-1158 in the first half of 2016

Selected Third Quarter 2015 Financial Results

Research and development expenses were $6.8 million for the three months ended September 30, 2015, compared with $3.9 million for the same period in the prior year. The increase of $2.9 million was primarily attributed to higher expenses associated with the continued advancement of CB-839 and investments in the Company’s arginase inhibitor program.
General and administrative expenses were $2.2 million for the three months ended September 30, 2015, compared with $1.3 million for the same period in the prior year. The increase of $0.9 million was primarily due to higher employment-related expenses, including stock-based compensation expense and professional service fees associated with operating as a publicly-traded company.
Net loss for the three months ended September 30, 2015 was $8.9 million.

Financial Guidance for 2015

Calithera is updating its guidance of its cash, cash equivalents and investments to be at least $70 million at the end of 2015, exclusive of any license milestone payments or funds arising from any additional new collaborations or partnerships, equity financings or other new sources.

On November 08, 2015 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that it will announce new clinical data from the solid tumor expansion cohorts of its lead anti-cancer therapeutic candidate, CB-839, at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference on Molecular Targets in Boston, Massachusetts (Press release, Calithera Biosciences, NOV 8, 2015, View Source;p=RssLanding&cat=news&id=2110182 [SID:1234508340]). CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor in phase I clinical trials. The data support earlier findings of the clinical activity, tolerability and unique mechanism of action of CB-839 in patients with solid tumors, as well as show one partial response according to RECIST criteria.

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The new data to be presented by Funda Meric-Bernstam, MD, from MD Anderson Cancer Center (Abstract #C49), demonstrate stable disease across a variety of tumor types, as well as a single agent partial response (PR, on study >5 months) in a renal cell carcinoma (RCC) patient. This patient showed a 32% reduction in target lesions by RECIST with generalized shrinkage of lymph node metastases. Among the fifteen evaluable patients with RCC, nine (60%) had stable disease lasting at least three cycles (63 days) or a partial response, with four patients remaining on study. Among efficacy-evaluable patients across a range of tumor types treated on the current dosing schedule of twice-daily with food, 22 of 50 patients (44%) experienced stable disease or better. Five stable disease patients currently on study have been treated with CB-839 for over 8 months without progression (2 triple negative breast cancer, 1 RCC, 1 mesothelioma and 1 IDH1 mutant chondrosarcoma).

"We are very encouraged by these findings in that they reinforce the published safety and efficacy profile of CB-839. We believe that this first partial response in solid tumors points to the potential of our novel agent’s efficacy in renal cell carcinoma, and we look forward to sharing data as our single agent and combination studies mature," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are currently expanding enrollment of CB-839 as a monotherapy in renal cell carcinoma patients, as well as dosing CB-839 in combination with everolimus."

The Phase 1 multi-center open label dose escalation study was designed to evaluate the safety and tolerability of CB-839 in locally advanced, metastatic and/or refractory solid tumors. Oral CB-839 was administered in doses of 100 mg to 1000 mg, in 21 day cycles using one of two regimens: TID or BID with food. As of October 1, 2015, 98 patients were enrolled in the solid tumor study (32 TID, 66 BID with food) and evaluable for safety; 77 were evaluable for efficacy. All future patients enrolled to the study will be dosed on the BID with food regimen.

Safety Data

Among 98 patients evaluable for safety, a maximum tolerated dose has not been established. CB-839 was generally well tolerated with the majority of treatment-emergent adverse events being mild to moderate, Grade 1/2 and reversible. Among patients in the BID with food regimen, 4.5% (3/66) experienced a Grade 3/4 adverse event suspected to be related to CB-839 and 3% discontinued due to drug-related adverse events (2/66). The rate of Grade 3 alanine aminotransferase (ALT) elevations of 1.5% (1/66) in the BID with food cohort was substantially reduced relative to that observed in the TID cohort 16% (5/32).

In addition, a preclinical poster was presented by Calithera’s collaborators. Details for the presentation are as follows:

Targeting glutamine metabolism in colorectal cancers with PIK3CA mutations

Abstract #C115
Zhenghe John Wang, Ph.D., Case Western Reserve University
Poster Session C

On November 8, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported that interim results from the company’s ongoing Phase 1 clinical trial of RXDX-105, the company’s orally-available, small molecule multikinase inhibitor with potent activity against such key targets as RET and BRAF, were presented at the 27th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts (Press release, Ignyta, NOV 8, 2015, View Source [SID:1234508112]).

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"We are excited by the data from our Phase 1 clinical trial of RXDX-105, including the overall safety profile and the recent partial response in a non-small lung cancer patient," said Pratik Multani, M.D., Chief Medical Officer of Ignyta. "We believe we are close to determining the recommended phase 2 dose (RP2D) and we look forward to further study of this product candidate in cancer histologies and molecular alterations of interest."

The dose escalation clinical trial was 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 RXDX-105 in patients with advanced or metastatic solid tumors that were not selected based on any molecular alteration.

As of the October 26, 2015, data cut-off for the presentation, the findings showed:

A total of 41 patients with a range of solid tumors were dosed in the clinical trial;
RXDX-105 was well tolerated to date:

The most frequent treatment-emergent adverse events were fatigue, vomiting, nausea, decreased appetite, constipation, diarrhea, hypertension and muscle spasms;

Three Grade 3 dose-limiting toxicities were observed: maculopapular rash, fatigue and diarrhea, each of which resolved upon study drug interruption;

There were no treatment-related serious adverse events. Two Grade 4 adverse events had occurred, consisting of intestinal obstruction and anemia, neither of which was considered to be treatment-related. No Grade 5 treatment-related adverse events or cumulative adverse events were observed;

The MTD and RP2D had not yet been determined;

Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to further increase exposure;

Exposure was reaching levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and

Tumor regression was observed in six patients treated with 275 mg, including one confirmed partial response (40% reduction) in a patient with non-small cell lung cancer with a KRAS G12C mutation. Two additional patients with thyroid cancer and squamous cell lung cancer exhibited reductions of 20% and 27%, respectively. In patients with tumor regression, there appears to be an exposure/response correlation.

On Monday, November 9, 2015, Ignyta will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the materials presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium. The company’s SEC filings can be found on the company’s website at www.ignyta.com and on the SEC’s website at www.sec.gov.

At the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, Ignyta also presented a poster relating to the potent RET inhibitory activity of RXDX-105 in multiple preclinical models of RET-rearrangement driven cancer. This poster is available on the company’s website at www.ignyta.com.

On November 8, 2015 ImmunoGen, Inc. (Nasdaq: IMGN), a biotechnology company that develops targeted anticancer therapeutics using its antibody-drug conjugate (ADC) technology, reported findings with mirvetuximab soravtansine, its novel folate receptor alpha (FRα)-targeting ADC product candidate, being presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (abstract #C47) (Press release, ImmunoGen, NOV 8, 2015, View Source [SID:1234508113]). Analysis of the association between the amount of FRα present on patient cancer cells and response to treatment with mirvetuximab soravtansine found nine of ten (90%) patients with high levels of FRα had an objective response on treatment.

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"These early findings are highly encouraging as they underscore the potential of mirvetuximab soravtansine to make an important difference for patients with ovarian cancer," said Dr. Charles Morris, chief development officer. "The data are from patients with heavily pretreated platinum-resistant ovarian cancer, which is a difficult disease to treat. We will be assessing mirvetuximab soravtansine as single-agent therapy for patients with pretreated FRα-positive ovarian cancer in our FORWARD I trial, a study we intend to use for registration purposes."

The findings presented today are from an analysis of 20 efficacy-evaluable patients with platinum-resistant ovarian cancer who received mirvetuximab soravtansine in Phase 1 testing at its selected dose. Patients were categorized as having high, medium or low amounts of FRα on their cancer cells.1 Enrollment criteria for the clinical study required all patients to have at least low expression.

Nine of the ten patients with high FRα expression had an objective response (2 complete responses/CRs, 7 partial responses/PRs by RECIST 1.1 criteria). Six of these responders remained on treatment for at least 24 weeks.

The six patients with medium expression all had tumor regression. One patient had an objective response (unconfirmed PR) and one had tumor shrinkage with new lesion formation (mixed response/MR). An additional patient remained on treatment for more than six months but did not have an objective response.

Four patients had low expression and none had an objective response. One patient was still on treatment at the time of data cut off for presentation.

The ORR was 50% for all 20 efficacy-evaluable patients. Among all 22 patients evaluable for tolerability, the majority of adverse events reported were low grade (grade 1 or 2), with diarrhea, blurred vision, vomiting, fatigue, and nausea the most common treatment-emergent events reported ( > 30% of patients).

ImmunoGen anticipates reporting mature data from the full 46-patient cohort in this study at a medical meeting in 2016.

The FORWARD I Trial

ImmunoGen’s FORWARD I trial will assess mirvetuximab soravtansine as single-agent therapy for the treatment of ovarian cancer previously treated with three to four prior regimens. Patients will have medium or high expression of FRα to qualify for enrollment in this Phase 2 study. Patient enrollment is expected to start in late 2015.

About Mirvetuximab Soravtansine

Mirvetuximab soravtansine (IMGN853) is a FRα-targeting ADC developed and wholly owned by ImmunoGen. It comprises a FRα-binding antibody conjugated to DM4, a potent cancer-killing agent created by ImmunoGen for use in ADCs. The antibody serves to target the DM4 specifically to FRα-positive cancer cells which the DM4 can then kill. FRα is highly expressed on many cases of epithelial ovarian cancer.2 It also is highly expressed on other types of solid tumors including endometrial cancer and some non-small cell lung cancers.

About Ovarian Cancer

Each year, there are approximately 21,300 new cases of ovarian cancer diagnosed in the US and more than 14,200 women die from the disease.3 Once the cancer has been treated with several lines of combination regimens, patients may be treated with single-agent therapy, which typically have response rates around 15-20%.4