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Endocyte Presents Data on Two Lead Clinical Programs at European Society for Medical Oncology (ESMO) 2016 Congress

On October 10, 2016 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported that it has presented poster updates on its two lead clinical programs at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress, being held in Copenhagen, Denmark October 7-11, 2016 (Press release, Endocyte, OCT 10, 2016, View Source [SID:SID1234515710]).

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"We are pleased that both EC1456 and EC1169 have shown anti-tumor activity during the dose escalation phase of their respective trials, even in patients not specifically identified as positive for the drug targets," said Mike Sherman, president and CEO at Endocyte. "The activity we’ve seen to date with EC1169 in prostate cancer patients is particularly exciting, with our first confirmed radiologic partial response (PR). This quarter we expect to move the 6.5 mg/m2 dose into the expansion phase of the study where we will evaluate EC1169 in patients selected as prostate specific membrane antigen (PSMA)-positive using our companion imaging agent, EC0652. We have also moved on to the expansion phase of the EC1456 trial, using our companion imaging agent etarfolatide to select folate receptor (FR)-positive non-small cell lung cancer (NSCLC) patients."

"Despite the current therapy options available for prostate cancer patients, there remains a need for safe and effective alternatives for these patients following treatment with hormone therapies," stated Michael J. Morris, M.D., Associate Professor, Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York. "The disease is more challenging to treat at this stage, so the safety data, and at least the preliminary efficacy data, which we’re seeing with Endocyte’s PSMA-targeted agent is encouraging. I look forward to further exploring this novel drug in patients with metastatic prostate cancer."

EC1169 Poster #731P – Phase 1 Study of the PSMA-Targeted Tubulysin Small-Molecule Drug Conjugate EC1169 in Patients with Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Study Update

Data presented in this poster showed that total target tumor burden reduction was observed in 4 of the 6 patients with measurable soft tissue disease treated at doses of 3.8 mg/m2 and higher. One of these patients demonstrated the first confirmed radiologic partial tumor response (PR) as measured by RECIST 1.1 criteria. Two patients also demonstrated confirmed prostate specific antigen (PSA) reductions of greater than 50%, one of whom went on to demonstrate the PR. After observing toxicity at 8.5 mg/m2, the company is in the process of confirming 6.5 mg/m2 as the highest clinical dose. EC1169 was well tolerated without causing dose-limiting hematologic toxicity frequently associated with traditional chemotherapy. Primary toxicities included fatigue and gastrointestinal (GI) toxicity; predominantly grade 1 and 2, reversible and responsive to simple medication.

EC1456 Poster #395P – Dose Escalation Phase 1, Safety and Pharmacokinetic Study of the Folate Receptor-Targeted Drug Conjugate EC1456 in Advanced Cancer Patients: Study Update

A dose of 6.0 mg/m2 was established as the maximum twice per week dose, administered 2 weeks out of a 3 week cycle, which is being used in the expansion phase of the trial in FR-positive NSCLC patients. EC1456 was well tolerated, with primary toxicities including fatigue, GI toxicity, and electrolyte disturbance; predominantly grade 1 and 2, reversible and responsive to simple medication. In spite of the inclusion of patients who were not selected as positive for the targeted FR, most patients demonstrated stable disease as best response and several patients demonstrated a reduction in target tumor volume.

About EC1169 and EC0652

EC1169 is an investigational therapeutic SMDC constructed of a high affinity PSMA-targeting ligand conjugated through a releasable linker system to a potent cytotoxic microtubule inhibitor, tubulysin B hydrazide (TubBH). The high affinity of EC1169 for PSMA allows for the active and specific delivery of TubBH to PSMA-expressing cancer cells, while minimizing exposure to normal cells. PSMA is known to be highly expressed on the majority of prostate cancers with limited expression on normal tissues.

The PSMA-targeted companion imaging agent EC0652 is being co-developed to characterize whole body PSMA expression in real time, to identify patients most likely to benefit from EC1169 therapy. EC1169 and EC0652 are currently being evaluated in a phase 1 study in patients with metastatic, castration-resistant prostate cancer (mCRPC) (ClinicalTrials.gov Identifier: NCT02202447).

About EC1456 and etarfolatide

EC1456 is an investigational therapeutic SMDC constructed of folic acid conjugated through a spacer and releasable linker system to a potent cytotoxic microtubule inhibitor, TubBH. The high affinity of the folic acid ligand for the FR allows for the active and specific targeting of EC1456 to FR-expressing cancer cells. The FR is highly expressed in several epithelial cancers (e.g. ovarian, NSCLC) but is expressed at low levels in most normal tissues.

Etarfolatide is an FR-targeted companion imaging agent being co-developed to characterize whole body FR expression in real time, to identify patients most likely to benefit from EC1456 therapy. EC1456 and etarfolatide are currently being evaluated in a phase 1 study in patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT01999738).

Corvus Pharmaceuticals Announces Biomarker Findings from Phase 1/1b Study of Lead Oral Checkpoint Inhibitor CPI-444 Presented at ESMO 2016 Congress

On October 10, 2016 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported biomarker findings from its ongoing Phase 1/1b study of CPI-444 as a single agent and in combination with Genentech’s TECENTRIQ (atezolizumab),‎ a fully humanized monoclonal antibody targeting protein programmed cell death ligand 1 (PD-L1). CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. The data were presented today in a poster session by Ian McCaffery, Ph.D., vice president, Translational Sciences at Corvus, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress at the Bella Center in Copenhagen, Denmark.

"The initial part of our Phase 1/1b trial was designed to provide data on optimum dosing, safety and relevant biomarkers, and we have achieved that goal. We have completed enrollment in the dose-selection part of the trial, which enrolled 48 patients in four cohorts. We now have a solid understanding of dose, schedule, pharmacodynamic parameters and biomarkers," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "We have selected the optimum single agent and combination dose of CPI-444 for the disease-specific expansion stage of the trial, which is now enrolling patients at 30 centers in the United States, Canada and Australia. We plan to present preliminary efficacy data from the dose-selection part of the study later this year."

Results presented showed:

Seven of seven patients receiving CPI-444 100 mg twice daily had sustained, complete blockade of peripheral blood lymphocyte A2A receptors.
Plasma levels of CPI-444 of 2 mcg/ml resulted in complete saturation of A2A receptors in peripheral blood lymphocytes.
Treatment-related increases in cytotoxic T-lymphocytes that were both PD-1-positive and CD8-positive (double positive) provided evidence of immune activation of peripheral blood lymphocytes. Previous research from others has shown that PD-1, CD8 double positive T-cells are associated with anti-tumor immune responses.
In 14 patients tested to date, increases in PD-1, CD8 double positive T-cells were observed in seven of seven patients receiving single agent CPI-444 100 mg twice daily, in one of three patients receiving single agent CPI-444 200 mg once daily, and in three of four patients receiving CPI-444 50 mg twice daily combined with TECENTRIQ.
CPI-444 has been well tolerated to date, with one patient experiencing a possibly drug related serious adverse event.
Based on these and other data, Corvus has selected an oral dose of 100 mg twice daily for 28 days for both the single agent and combination arms of the second part of the trial.
ABOUT CPI-444
CPI-444, Corvus’ lead checkpoint inhibitor, is an adenosine A2A receptor antagonist. It is designed to disable a tumor’s ability to subvert attack by the immune system by inhibiting adenosine in the tumor microenvironment. CPI-444 is a small molecule that is taken orally. It is in development as an immuno-oncology therapy for the treatment of patients with solid tumors.

ABOUT THE PHASE 1/1B TRIAL
The Phase 1/1b trial is designed to examine the activity of CPI-444 as a single agent and in combination with Genentech’s TECENTRIQ (atezolizumab), an anti-PD-L1 antibody. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed all standard therapies are eligible.

The first part of the study (dose-selection) included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with TECENTRIQ). A treatment cycle is 28 days. Based on safety and biomarker analyses, an optimum single agent and combination dose were selected. The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts, and CPI-444 in combination with TECENTRIQ in five additional matched disease-specific cohorts. Corvus expects that each of these 10 cohorts will initially enroll 14 patients, but each cohort may be expanded based on efficacy.

HELSINN GROUP INTRODUCES HELSINN INVESTMENT FUND

On October 10, 2016 Helsinn, the Swiss Pharmaceutical Group focused on building quality cancer care, reported the Helsinn Investment Fund S.A. ("the Fund"), a fund focused on early-stage investment opportunities in areas of high unmet patient need (Press release, Helsinn, OCT 10, 2016, View Source [SID:SID1234515692]). With an initial investment commitment of three years, followed by up to five years via follow-on rounds, the fund will have a total commitment of $50 million. The Helsinn Investment Fund is incorporated in Luxembourg and fully owned by the Helsinn Group.

In the Group’s 40th year of operations, Helsinn has launched this fund applying its fundamental core values of quality, integrity and respect, and drawing on 40 years’ expertise in research and development and commercialization of therapeutic candidates in cancer care, pain and inflammation and gastroenterology. The Fund aims to help companies working across a range of areas in healthcare to develop early-stage technologies into commercial solutions that will impact health-related quality of life of patients.

The Fund plans to make select investments in companies with early stage technologies and assets in a range of areas including cancer therapeutics and diagnostics, cancer supportive care, metabolic and gastrointestinal disorders, and dermatology conditions, across biotechnology, pharmaceuticals, medical devices and food supplements.

Through the Fund, Helsinn will invest directly in 10 to 15 companies, providing scientific and clinical strategy guidance, operational and board support alongside ongoing investment.

The Fund will focus on companies with strong science and technology which have achieved at least preclinical proof of concept, and ideally with clinical data. Before committing to an investment, the Fund performs stringent due diligence and expects the highest standards from experienced management teams, realistic development plans and a clear go-to-market strategy. Underpinned by clear value propositions, the Fund is confident of achieving positive financial returns. To date, the Fund has made investments in companies including Mei Pharma Inc., US, OncoResponse Inc, US, QuantuMDx UK.

The Fund will be steered by a highly experienced Board of Directors including Riccardo Braglia, Helsinn Group Vice Chairman and Chief Executive Officer, Luigi Caletti, Financial Advisor of Helsinn Group, Dr Francesco Granata, Consultant, Senior Advisor at Warburg Pincus International LLC and Chairman of Circassia Plc and Betty Prudhomme, Senior Vice President, Tax Department, SGG Luxembourg.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, commented: "Early stage medical innovation is the lifeblood of our industry and the future for patient care. Without critical early financial support, promising businesses cannot advance this innovation towards commercialisation.

"We’ve created Helsinn Investment Fund to help support these companies. Helsinn’s 40 years’ experience working to improve the daily lives of people affected by a range of chronic diseases has shown us how much we depend on innovation. We look forward to announcing future investments as we build the portfolio."

The Investment Advisory team will be led by Riccardo Braglia MBA and Luigi Caletti MAA, and managed by Roberto De Ponti Pharm. D., Dr. Francesco Granata M.D., Hanna E. Kleczkowska, Ph.D., and Sandra van Essche, J.D., as well as Karin Hehenberger, M.D., Ph.D.

The company has applied to register as SICAR in Luxembourg under the supervision of the Commission de Surveillance du Secteur Financier (CSSF).

Daiichi Sankyo Presents Late-Breaking Phase 1 Data for Novel Investigational HER2-Targeting Antibody Drug Conjugate DS-8201a in T-DM1 Pre-Treated Breast Cancer at the ESMO 2016 Congress

On October 9, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported safety and preliminary efficacy data from a phase 1 study of DS-8201a, a novel investigational HER2-targeting antibody drug conjugate, which suggest that it was well-tolerated with no dose-limiting toxicities (Press release, Daiichi Sankyo, OCT 9, 2016, View Source [SID:SID1234515728]). These results, from the dose escalation part of a two-part phase 1 study of DS-8201a, will be presented today during a late-breaking poster discussion session at the ESMO (Free ESMO Whitepaper) 2016 Congress, the annual meeting of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).

DS-8201a is an investigational antibody drug conjugate comprised of a humanized anti-HER2 antibody attached by a peptide linker to a novel topoisomerase I inhibitor (DXd) payload, utilizing Daiichi Sankyo’s proprietary payload and linker-payload technology.

Preliminary overall efficacy results in 20 evaluable patients demonstrated an objective response rate of 35 percent (seven partial responses) and disease control rate of 90 percent, including 12 patients previously treated with ado-trastuzumab emtansine (T-DM1) and five patients with HER2 low expression (IHC2+/FISH- or IHC1+). In 15 patients with HER2+ disease defined as IHC3+ or IHC2+/FISH+, the disease control rate was 100 percent. Seventeen patients are still on treatment, and five of the first 10 patients have been under active treatment (0.8 to 6.4 mg/kg) for more than 24 weeks. Median progression free survival has not been reached.

"Despite recent advances in treating HER2+ breast and gastric cancer, there still remains a large unmet need for patients with HER2+ disease whose tumors are no longer controlled by currently approved targeted HER2 treatments or for tumors that express low HER2," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These preliminary results are compelling and warrant further clinical evaluation of DS-8201a in several different patient populations expressing HER2."

"The components that make up DS-8201a are unique from any other antibody drug conjugate currently in clinical development and may explain the clinical activity observed at such an early phase of development," said José Baselga, MD, PhD, Physician-in-Chief and Chief Medical Officer at Memorial Sloan Kettering Cancer Center, New York, NY. "While the results of this study provide important preliminary proof-of-concept for the novel mechanism of action of DS-8201a, additional research will be needed to further confirm these findings."

A total of 22 patients (16 breast cancer, 5 gastric cancer, 1 gastroesphageal junction adenocarcinoma) were treated in the dose escalation part of the study. The maximum tolerated dose was not reached (0.8-8.0 mg/kg given every three weeks) and there have been no dose-limiting toxicities at pharmacologically-active exposure and a favorable pharmacokinetic profile. Seven grade 3 adverse events were seen in three patients (1 hypokalemia, 1 anemia, 1 neutrophil count decreased, 2 lymphocyte count decrease, 1 ALP increase and 1 cholangitis). Most common adverse events were mild or moderate gastrointestinal and hematological events.

HER2+ Breast Cancer Subgroup Analyses
A total of 18 patients enrolled in the study received one or more prior anti-HER2 therapies (18 received trastuzumab, 13 ado-trastuzumab emtansine, 5 pertuzumab, 4 lapatinib). In 12 evaluable HER2+ breast cancer patients previously treated with ado-tratuzumab emtansine (T-DM1), the objective response rate was 42 percent with a disease control rate of 92 percent.
"It is impressive that DS-8201a showed activity in these patients since many were heavily pre-treated with more than one HER2-targeting agent including T-DM1, and some with very substantial tumor load or large tumors," said Kenji Tamura, MD, PhD, Chairman, Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan and lead investigator of the study. "This finding will be further evaluated in the second part of this study where one cohort will include only advanced breast cancer patients previously treated with T-DM1."

About DS-8201a
Pre-clinical models have demonstrated that DS-8201a has a unique mechanism of action (MOA) where it selectively binds to the HER2 receptor on a tumor cell surface, triggering an antibody-dependent cell cytotoxic (ADCC) response.1 DS-8201a is then internalized via endocytosis (transportation into cells by an energy-using process) and the intracellular lysosomal enzymes break down the peptide to release the DXd payload, which then inhibits topoisomerase I activity, causing DNA damage and cell death.1
The linker-payload combination of DS-8201a allows for a higher drug-to-antibody ratio (DAR) of about 8 compared to a DAR of about 3.5 seen with ado-trastuzumab emtansine (T-DM1).1 The higher DAR of DS-8201a may help target low expressing HER2 tumors by supplying more payload per antibody to a tumor.1

About the DS-8201a Phase 1 Study
DS-8201a, given as an intravenous infusion every three weeks, is currently being evaluated in an open-label two-part phase 1 study in patients with advanced/unresectable or metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma, or other solid tumors that is/are refractory to or intolerable with standard treatment or for which no standard treatment is available.
The primary objective of part 1 of the study (dose escalation) is to assess the safety and tolerability of DS-8201a and determine the maximum tolerated dose (MTD). Secondary objectives include evaluating the pharmacokinetics, efficacy and human anti-human antibody (HAHA) against DS-8201a.
The second part (dose expansion) of the ongoing phase 1 clinical trial is enrolling patients in Japan and the United States into one of four cohorts: patients with HER2+ breast cancer previously treated with T-DM1; patients with HER2+ gastric or gastroesophageal junction adenocarcinoma previously treated with trastuzumab; patients with HER2 low expressing breast cancer; and patients with other solid cancers that express HER2. For more information about the study visit ClinicalTrials.gov.

Unmet Need in HER2+ Metastatic Breast Cancer
HER2 (known as human epidermal growth factor receptor 2) is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells.2 About one in five breast cancers overexpress the HER2/neu gene, which causes these cancers to grow more aggressively.2 To be considered HER2+, cancer cells are tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH).2 IHC test results are reported as: 0, IHC1+, IHC2+ or IHC3+. A finding of IHC3+ is considered HER2+.2 A finding of IHC2+ is borderline and typically is confirmed by a positive FISH test.2
Several unmet needs remain today in HER2+ metastatic breast cancer. Many tumors advance to the point where no currently approved HER2-targeted treatment continues to control the disease.3 Additionally, there are no existing options indicated for HER2 low expressing tumors (IHC2+/FISH- or IHC1+) as well as HER2 heterogeneously expressing tumors (tumors with some tumor cells having high HER2 expression and some having low HER2 expression), which generally have poor prognosis.1,4

TRACON Pharmaceuticals Presents Final Updated Phase 1b Results for TRC105 in Combination with Inlyta® in Renal Cell Carcinoma at the ESMO 2016 Congress

On October 9, 2016 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported final updated results from a Phase 1b clinical trial combining TRC105 with Inlyta (axitinib) in patients with advanced or metastatic renal cell carcinoma (RCC) (Press release, Tracon Pharmaceuticals, OCT 9, 2016, View Source;p=irol-newsArticle&ID=2210295 [SID:SID1234515718]). Data were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark. Preliminary data from this trial were previously presented at the Kidney Cancer Association meeting in November 2015 and the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium in February 2015.

The open-label dose escalation and expansion Phase 1b study enrolled a total of 18 patients (17 of whom were evaluable for response) who had received at least one prior line of therapy with a VEGF receptor tyrosine kinase inhibitor (VEGFR TKI). The median number of prior therapies in the group was three with a range of one to six. All patients in the trial received a combination of TRC105 and Inlyta. Data are summarized in the table below.

Summary of Phase 1b Results for TRC105-Inlyta Combination
Patients ORR Stable
Disease Overall Disease
Control Median PFS Median PFS in Clear Cell
RCC Subset (n=12)
N = 17 29%
(5/17) 59%
(10/17) 88%
(15/17) 11.3 months 11.3 months
For comparison, the objective response rate (ORR) seen in the large subgroup of VEGFR TKI-refractory patients treated with Inlyta (n=194) in the Inlyta AXIS Phase 3 study in second line clear cell RCC patients (a separate trial) was 11.3%, and median progression-free survival (PFS) was 4.8 months.

All patients in TRACON’s Phase 1b study have now completed treatment and the randomized Phase 2b TRAXAR clinical trial of TRC105 in combination with Inlyta is currently enrolling patients with advanced or metastatic RCC. TRACON expects top-line data from the TRAXAR study to be available in the first half of 2017. A Trials-in-Progress poster for the TRAXAR study was also presented at the meeting. The poster presentations are available on the Publications page under the News section of the TRACON website at www.traconpharma.com.

The following key additional data from the Phase 1b study were also presented at the meeting:

The recommended Phase 2 dose of TRC105 of 10 mg/kg dosed weekly was well-tolerated in combination with Inlyta and no dose limiting toxicities were observed.
The most common adverse events were low grade epistaxis, headache, fatigue, diarrhea, and gingival bleeding.
The Inlyta dose was escalated from 5 mg BID to 7 mg BID in 22% of patients and to 10 mg BID in 11% of patients.
Serum concentrations of TRC105 above target concentrations were maintained continuously at the 8 mg/kg and 10 mg/kg TRC105 dose levels.
Plasma levels of TGF-b receptor 3 (betaglycan) at baseline were significantly higher in patients with a partial response, while levels of osteopontin were significantly lower at baseline for patients that achieved a partial response. Both markers correlated with time on study and their potential prognostic/predictive value are being investigated in the Phase 2b TRAXAR study.
About the TRAXAR Phase 2b Clinical Trial in RCC

The Phase 2b TRAXAR clinical trial is a multicenter, open-label, randomized clinical trial of TRC105 in combination with Inlyta versus Inlyta in patients with advanced or metastatic RCC. The primary endpoint of the Phase 2b study is progression-free survival. The company expects to enroll approximately 150 patients who have failed one prior VEGF inhibitor in the study. Patients may have also failed one prior mTOR inhibitor and one prior immunotherapy. For additional information on this clinical trial, please visit www.clinicaltrials.gov, identifier NCT01806064.

About TRC105 (carotuximab)

TRC105 (carotuximab) is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation, and also expressed on fibroblasts, a cell that causes fibrosis. TRC105 is currently being studied in multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis. For more information about the clinical trials, please visit TRACON’s website at View Source