On November 08, 2015 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported new results from its Phase 1 open-label, dose-escalation trial of LOXO-101, a selective inhibitor of tropomyosin receptor kinase (TRK) signaling molecules, and the first preclinical data for its RET and FGFR programs (Press release, Loxo Oncology, NOV 8, 2015, View Source [SID:1234508117]). The data are being presented at the 2015 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) in Boston.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Providing a LOXO-101 Phase 1 update, study investigators reported that, as of the October 20, 2015 data cutoff date, 30 patients with solid tumors refractory to standard therapy had been enrolled and treated, including six patients with cancers harboring TRK fusions. Three of the six patients with TRK fusion cancers had been on study sufficiently long for their first efficacy assessment, and all three had achieved an objective response at the first response assessment, as defined by standard RECIST criteria. All three of these patients remain in response and on study. The other three patients with TRK fusion cancers were recently enrolled and thus had not yet been evaluated for response as of the data cutoff date, though they all remain on study. In addition, LOXO-101 has been well tolerated, including the 100 mg twice-daily dose, which has been selected for Phase 2 study and has shown efficacy in TRK fusion patients. The majority of adverse events reported by investigators have been mild to moderate. A maximum tolerated dose (MTD) has not been defined, though near-term Phase 1 enrollment will focus on further characterizing the pharmacokinetics and safety of the 100 mg twice-daily dose dosing.

"The efficacy we are seeing for LOXO-101, at a well-tolerated dose, is as compelling as any I have seen in Phase 1," said David Hong, M.D., deputy chair and associate professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston and presenter of the LOXO-101 oral presentation. "As a community, we need to test for TRK fusions and make sure these patients find their way to a LOXO-101 study. I look forward to participating in the recently initiated Phase 2 trial."

"We are very encouraged by the rapid and dramatic responses we are seeing in TRK fusion patients, which demonstrate LOXO-101’s ability to effectively target these genetically defined tumors," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "As we look into 2016, we are focused on continuing to execute on our clinical development strategy for LOXO-101 and plan to release additional data from our Phase 1 study at a medical meeting next year. In addition, our preclinical posters show the progress we have made, with our partners at Array BioPharma, in developing other selective, purpose-built molecules with differentiated and best-in-class potential against highly actionable targets in oncology."

LOXO-101 Phase 1 Results
LOXO-101 is currently being evaluated in an ongoing dose-escalation Phase 1 trial in patients with solid tumors refractory to standard therapy. As of October 20, 2015, 30 patients with advanced cancer had been treated at five dose levels: 50 mg QD, 100 mg QD, 100 mg BID, 150 mg BID, and 200 mg QD. The median age of these patients is 55 (ranging from 28-76) and the median number of prior treatments was three (ranging from 0-11).

Safety Analysis
LOXO-101 has been well tolerated in the 30 patients treated as of October 20, 2015. Adverse events are reported regardless of attribution to study drug. Adverse events are generally consistent with those described after the last data cutoff of March 26, 2015, consisting of Grade 1 and 2 fatigue (33 percent), dizziness (30 percent), anemia (20 percent) and nausea (20 percent). Grade 3 adverse events reported included fatigue, anemia, abdominal pain, increased liver enzymes, delirium and syncope. No Grade 4 adverse events have been reported. The frequency of toxicities did not correlate with dose level. MTD has not yet been defined.

Efficacy Analysis
To date, six patients with cancers harboring TRK fusions have been enrolled, representing a broad range of tumor types: mammary analogue secretory cancer of the salivary glands (MASC) (n=2), soft tissue sarcoma, gastrointestinal stromal tumor, thyroid carcinoma, and non-small cell lung cancer. As of the October 20, 2015 data cutoff date, three patients had been evaluated for response, and all had achieved an objective response at first response assessment. A patient with soft tissue sarcoma harboring an LMNA-NTRK1 fusion remains on study for greater than eight months at a dose of 100 mg BID. This patient was the subject of a peer-reviewed research brief published in Cancer Discovery in July 2015. A patient with a gastrointestinal stromal tumor (GIST) harboring an ETV6-NTRK3 fusion remains on study for greater than four months at a dose of 150 mg BID. A patient with a MASC tumor harboring an ETV6-NTRK3 fusion remains on study for greater than three months at 100 mg BID. All three of these responding patients remain in response and on study as of October 20, 2015. The other three patients (thyroid carcinoma, non-small cell lung cancer, MASC) were recently enrolled and not yet evaluable for efficacy as of the data cutoff date.

On Monday, November 9, 2015, Loxo Oncology will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the LOXO-101 materials presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting. These materials will also be posted to the Loxo Oncology website.

Pipeline Program Updates
Loxo Oncology presented data from the company’s novel Rearranged during Transfection (RET) and Fibroblast Growth Factor Receptor (FGFR) programs showing potential best-in-class selectivity and target coverage. Loxo Oncology expects to advance a RET inhibitor as its next Investigational New Drug (IND) application.

Upcoming Milestones for Loxo Oncology
Loxo Oncology continues to make significant progress across its pipeline. Milestones in 2016 are expected to include:

Continued enrollment of the LOXO-101 Phase 2 global, multi-center, single-arm, open-label basket trial in adult patients with solid tumors that harbor a TRK fusion.
Presentation of additional data from the ongoing Phase 1 study of LOXO-101 at a medical meeting in 2016.
Initiate Phase 1 study of LOXO-101 in pediatric cancer patients, including an oral liquid formulation, in the first half of 2016.
Initiate Phase 1 study of a selective RET inhibitor in late 2016 or early 2017.

About LOXO-101
LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions. For additional information about both the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.

On November 8, 2015 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the first data from the dose-escalation portion of the ongoing Phase 1 study evaluating single agent AG-120, a first-in-class, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-1 (IDH1), in advanced solid tumors (Press release, Agios Pharmaceuticals, NOV 8, 2015, View Source;p=RssLanding&cat=news&id=2110176 [SID:1234508099]). The data are being presented today 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) in Boston. AG-120 is being developed in collaboration with Celgene.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Glioma, cholangiocarcinoma and chondrosarcomas are all extremely difficult-to-treat diseases with limited therapeutic options," said Howard Burris, M.D., Sarah Cannon Research Institute, an investigator for the study. "Today’s Phase 1 dose-escalation data are encouraging, as they confirm a well-tolerated safety profile and show signals of clinical activity that support further evaluation in patients with IDH1 mutant positive solid tumors."

"We are excited to present the first data from AG-120 in solid tumors as we explore the novel mechanism of action of our IDH inhibitors in these indications," said Chris Bowden, M.D., chief medical officer at Agios. "These early data suggest that inhibiting mutant IDH1 can alter the biology of these diseases, and we are committed to moving AG-120 forward into the next phase of clinical development."

This ongoing Phase 1 trial is assessing the safety and tolerability of AG-120 in advanced solid tumors, including glioma, intrahepatic cholangiocarcinoma (IHCC) and chondrosarcomas that harbor an IDH1 mutation in a dose-escalation phase followed by an expansion phase. As of September 3, 2015 (data cut-off), 62 patients have been treated with single agent AG-120, and 25 patients remain on treatment. Data reported at the meeting are from patients who received AG-120 administered from 200 mg to 1200 mg total daily doses in the dose-escalation arm. The median age of these patients is 56 (ranging from 23-88). Over half of the patients enrolled had high-grade tumors and received a median of three prior lines of therapy (ranging from one to six).

Safety Data

The safety analysis conducted for all 62 treated patients as of September 3, 2015 demonstrated that AG-120 was well-tolerated with a favorable safety profile in advanced solid tumors including glioma, IHCC and chondrosarcoma. Specifically the analysis showed:

No dose limiting toxicities have been observed.
The majority of adverse events reported by investigators were mild to moderate, with the most common being nausea, diarrhea, vomiting, anemia and QT prolongation.

The majority of serious adverse events (SAE) were disease-related.
A maximum tolerated dose (MTD) has not been reached.

Efficacy Data

Agios also analyzed efficacy data from 55 response-evaluable patients as of September 3, 2015, which showed:

Treatment with AG-120 showed substantial reduction of the oncometabolite 2-hydroxglutarate (2HG) in plasma and tumor tissue.
Imaging (magnetic resonance spectroscopy) results suggest that AG-120 can lower 2HG in the brain.

Chondrosarcoma: Seven of the 11 patients with IDH1 mutant positive chondrosarcoma had stable disease. Five of these patients maintained stable disease for six months or more. The six-month clinical benefit response rate was 5/9 or 56 percent.

IHCC: One out of 20 patients with IDH1 mutant positive IHCC had a partial response (PR) and 11 patients had stable disease. Six of these patients, including one with a PR and five with stable disease, maintained their response for six months or more. The six-month clinical benefit response rate was 6/14 or 43 percent.

Glioma: Ten out of 20 patients with IDH1 mutant positive glioma had stable disease. Four of these patients maintained stable disease for six months or more. The six-month clinical benefit response rate was 4/16 or 25 percent.
Other: One of the four patients with other IDH1 mutant positive solid tumors had stable disease.

Next Steps for AG-120 in Solid Tumors

Currently enrolling four expansion cohorts of 25 patients each, who receive the recommended dose of 500 mg of AG-120 once daily, with:
Low grade glioma with ≥ six months of prior scans to assess volumetric changes
Second-line cholangiocarcinoma
High grade (metastatic) chondrosarcoma
Other solid tumors with an IDH1 mutation
Initiate a randomized Phase 2 study of AG-120 in cholangiocarcinoma in 2016.

Investor Event and Webcast Information

Agios will host an investor event with Dr. Howard Burris today at 1:00 p.m. ET in Boston to review data presented at the conference. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for approximately 30 days following the presentation.

About Chondrosarcoma

Chondrosarcoma is a heterogeneous group of cancers that arise from cartilage in the bone and joint. It is the most common type of bone cancer with 700-1,000 people diagnosed per year in the U.S. IDH1/2 mutations occur in 40-50 percent of central chondrosarcomas. The prognosis is based on disease burden – for localized disease, there is curative potential with surgery, but metastatic disease has a low five-year survival rate. Radiation is not effective, and chemotherapy is of limited benefit and primarily used to convert non-resectable cancer to resectable. Treatment for metastatic disease is mainly palliative.

About Intrahepatic Cholangiocarcinoma (IHCC)

IHCC occurs within the liver, and the prognosis is worse than for other biliary tract tumors. The incidence of IHCC is increasing due to cirrhosis, alcoholic liver disease and hepatitis C. IHCC has a poor five-year survival rate, with 15-30 percent for local disease and 2 percent for metastatic disease. IDH1/2 mutations are present in approximately 25 percent of IHCCs. Surgery is the only chance for curing localized disease. Surgery, radiation and chemotherapy are palliative for metastatic disease.

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma). Common symptoms include memory disturbance, sensory impairment neurologic deficits and seizures. The long-term prognosis is poor with a five-year survival rate of 33 percent. Median survival is 12-15 months for glioblastoma and 2-5 years for anaplastic glioma. IDH1 mutations are highly prevalent.

About IDH Mutations and Cancer

IDH1 and IDH2 are two metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH increases production of an oncometabolite 2-hydroxyglutarate (2HG) that alters the cells’ epigenetic programming, thereby promoting cancer. 2HG has been found to be elevated in several tumor types. Agios believes that inhibition of the mutated IDH proteins may lead to clinical benefit for the subset of cancer patients whose tumors carry them.

On November 8, 2015 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called Accurins, reported data demonstrating the efficacy and tolerability of BIND’s Accurin platform with multiple anti-cancer agents (Press release, BIND Therapeutics, NOV 8, 2015, View Source [SID:1234508103]). These data, which were 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) held in Boston, November 5-9, 2015, describe the ability of Accurins to control the biodistribution of therapeutic payloads across multiple active anti-cancer agents, pathways and targets, which results in either improved efficacy, tolerability or both.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The four posters presented include preclinical and clinical pharmacokinetic data from BIND’s clinical stage Accurin compound, BIND-014; data from BIND’s preclinical stage Accurin, BIND-510; and new data from a previously unannounced feasibility study with Merck, demonstrating the potential value of an Accurin formulation of Merck’s proprietary AKT inhibitor, MK-2206.

"We believe data from these posters reinforce the flexibility of the Accurin platform to incorporate multiple therapeutic payloads and target them to sites of disease while limiting exposure to healthy tissue," said Andrew Hirsch, president and chief executive officer, BIND Therapeutics. "These data also demonstrate the ability of Accurins to create potentially best-in-class therapeutics, both with our proprietary product candidates as well as those of our collaborators, as demonstrated with the Merck AKT inhibitor MK-2206."

"The ability of our Accurin platform to overcome the challenges often associated with narrow therapeutic windows of otherwise powerful drugs is reinforced by these data," said Hagop Youssoufian, M.D., chief medical officer at BIND. "BIND-014 continues to demonstrate important and potentially differentiating points from docetaxel; BIND-510 exhibits promising pharmacokinetics, tumor accumulation, tolerability and anti-tumor activity across multiple tumor types in preclinical models; and the feasibility study with an Accurin formulation of Merck’s MK-2206 further validates the applicability of our Accurin platform to drugs with diverse mechanisms of action."

Posters presented at 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)

BIND-014

1. "Evaluation of total and encapsulated drug pharmacokinetics for BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in a phase 1 study"

BIND researchers and collaborators evaluated the pharmacokinetic (PK) profile of BIND-014 in 28 patients with advanced or metastatic cancer and determined that PK properties of BIND-014 are primarily due to retention of encapsulated docetaxel within the vascular compartment and controlled release of docetaxel. These characteristics together with PSMA targeting, potentially lead to greater tumor uptake and improved activity of BIND-014 compared to conventional solvent-based docetaxel.

BIND-014 was administered by a 60-minute intravenous infusion at doses ranging from 3.5-75 mg/m2 on Day 1 of a 21-day cycle.
Plasma concentrations of BIND-014 persisted for at least 48 hours at the higher dose levels.

Clearance was independent of the administered dose, indicating a linear dose-concentration relationship following a single intravenous administration.

The total concentration of BIND-014 found in circulation compared to the concentration of encapsulated docetaxel was similar, indicating that the majority of the circulating docetaxel was encapsulated in nanoparticles.

Results are consistent with the favorable tolerability profile of BIND-014 despite the markedly higher plasma concentrations for total BIND-014 compared to published data for docetaxel at similar doses.

BIND-014 displays a PK profile well differentiated from conventional docetaxel and consistent with retention of BIND-014 nanoparticles in the blood compartment and controlled release of docetaxel.

2. "Cardiovascular safety profile of BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in phase 1 and 2 studies"
BIND researchers determined that BIND-014, when administered on day 1 of a 21-day cycle with doses ranging from 3.5-75 mg/m2, was well tolerated at all doses studied and has the potential to become a safe antitumor agent without the cardiovascular effects typically associated with docetaxel.

For all 110 patients tested, the vast majority of ECG data collected remained in normal or clinically insignificant abnormal limits.
Vitals signs for heart rate, respiratory rate, and pulse were also within normal or clinically insignificant abnormal limits.
The incidence and severity of cardiovascular adverse events was low, with only seven patients experiencing drug-related cardiovascular adverse events ranging from grade 1-3. Patients dosed below 60 mg/m2 did not experience any drug-related cardiovascular adverse events.

BIND-510

1. "BIND-510 improves the pharmacokinetics, tolerability, tumor accumulation and tumor growth inhibition in preclinical models of cancer compared to vincristine sulfate"
BIND researchers demonstrated that BIND-510 exhibited differentiated PK, tumor accumulation, tolerability and anti-tumor activity compared to conventional vincristine (VCR). In addition, PSMA expression was demonstrated in the neovasculature in hematological cancers, further supporting the feasibility of developing BIND-510 as a targeted clinical therapy with the potential for reduced toxicity and improved anti-tumor activity compared to currently available treatments.

BIND-510 had a PK profile differentiated from VCR that results in increased accumulation of vincristine at the tumor, and increased tumor growth inhibition in multiple xenograft models.

BIND-510 accumulated in nasopharyngeal carcinoma tumors at an 8-fold higher concentration than VCR, and was shown to be more tolerable than VCR.

Single dose BIND-510 administered to mice with nasopharyngeal and breast carcinoma xenografts at the maximum tolerated dose (MTD) for VCR (1.5 mg/kg) resulted in a longer tumor growth delay compared to VCR.

Due to improved tolerability, BIND-510 was able to be administered at higher doses, resulting in complete responses in some mice, and even longer tumor growth delay than VCR or BIND-510 dosed at 1.5 mg/kg.

PSMA targeting of BIND-510 in PSMA-expressing prostate cancer tumor xenografts resulted in a tumor growth inhibition (TGI) of (79%) compared to non-targeted VCR nanoparticles which caused a 47 percent TGI at the same VCR dose level.
Non-small cell lung cancer tumor xenografts that are insensitive to VCR at MTD are sensitive to BIND-510 when administered at higher dose levels.

PSMA immunostaining was detected in the neovasculature of 27.5 percent lymphoma tumors and 35 percent of bone marrow malignancies analyzed.

MK-2206 (BIND-2206)

1. "Accurins improve the pharmacokinetics, pharmacodynamics, tolerability and anti-tumor activity of the AKT inhibitor MK-2206"
BIND researchers and collaborators at Merck demonstrated that Accurin formulations of MK-2206 (BIND-2206) developed with varying in vitro release rates had differentiated PK, increased tumor exposure, improved tolerability and a prolonged duration of target inhibition compared to the parent compound. Improving these biological attributes led to a significantly enhanced anti-tumor efficacy in an ovarian cancer model and tumor regressions in a prostate cancer model. In addition, the altered bio-distribution resulted in prolonged target engagement in tumor tissue and enhanced efficacy compared to the parent MK-2206, suggesting that Accurin formulations of the AKT inhibitor (BIND-2206) may provide improved tolerability and anti-tumor activity in a clinical setting.

BIND-2206 Accurins significantly altered the pharmacokinetic parameters of MK-2206 in female nude mice following acute administration.

Dosed at maximum feasible dose, BIND-2206 Accurins significantly enhanced tolerability measured by percent survival and prevented hyperglycemic blood glucose levels in mice following acute administration.

BIND-2206 Accurins displayed significant tumor regressions in human prostate cancer models compared to MK-2206.

BIND-2206 Accurins displayed significant anti-tumor activity in human ovarian cancer model compared to MK-2206.

BIND-2206 Accurins as a single agent did not improve efficacy in a HER2 overexpressing breast cancer model but displayed significant and prolonged inhibition of the target in the tumor. This suggests that anti-tumor efficacy is model specific and that a combination strategy in breast cancer may be advantageous.

On November 8, 2015 Ignyta, Inc. (Nasdaq: RXDX) ("Ignyta"), a precision oncology biotechnology company, reported the exclusive license of worldwide rights relating to Eli Lilly and Company’s taladegib oncology development program in exchange for an upfront payment of $2.0 million in cash and the issuance to Lilly of approximately 1.2 million shares of Ignyta’s common stock (Press release, Ignyta, NOV 8, 2015, View Source [SID:1234509530]). Taladegib is a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved clinical proof-of-concept and a recommended Phase 2 dose based on results from prior clinical studies. Ignyta also licensed exclusive worldwide rights to the topical formulation of taladegib, which is a late preclinical program being developed for the potential treatment of patients with superficial and nodular basal cell carcinoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Concurrently with the license, Ignyta entered into a stock purchase agreement with Lilly under which Lilly will purchase a further 1.5 million shares of Ignyta common stock at a price of $20 per share in a private placement. Lilly has agreed not to sell or otherwise transfer any of the shares acquired from Ignyta until May 10, 2016, and Ignyta is required to register the resale of the shares issued to Lilly with the Securities and Exchange Commission (SEC) prior to such date.

Under the license agreement, Ignyta is obligated to pay to Lilly development and sales milestones related to taladegib products totaling up to approximately $38 million (a portion of which may be paid in Ignyta equity), along with royalties on net sales of taladegib products. Ignyta also granted back to Lilly exclusive rights to develop and commercialize taladegib-containing products in combination with certain Lilly compounds. Lilly is obligated to pay to Ignyta a royalty on net sales of such combination products it commercializes. Further financial terms were not disclosed.

"We are pleased to be working with Ignyta to further the development of taladegib and explore its potential to help patients across multiple tumor types," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "Lilly continues to raise the bar on innovation by leveraging external relationships and expertise. Moreover, we are looking forward to working with Ignyta on potential combination therapies with other Lilly compounds."

"The exclusive license from Lilly of this clinical program with demonstrated compelling Phase 1 activity is well aligned with our strategic vision of developing first-in-class and/or best-in-class therapeutics that can potentially eradicate residual disease in precisely defined patient populations," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "This new targeted oncology program is a hedgehog/smoothened antagonist that complements our pipeline well and provides us with exciting potential monotherapy and combination therapy approaches across multiple solid tumor indications. We are grateful to Lilly for sharing Ignyta’s precision oncology vision and recognizing the strong strategic fit of taladegib with our pipeline and capabilities, which led to its $30 million investment in the company."

On November 8, 2015 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative drug candidates for the treatment of cancers, reported that its collaborator Aurigene presented preclinical data from two programs 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) including: (1) CA-170 (previously AUPM-170), a first-in-class oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), and (2) the interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor program. Curis recently exercised options to license both these programs under a collaboration agreement with Aurigene established earlier this year (Press release, Curis, NOV 8, 2015, View Source [SID:1234508105]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CA-170 (PD-L1/VISTA antagonist) presentation:

Aurigene presented a poster entitled "First-in-class orally available immune checkpoint antagonists for cancer therapy" on Friday, Nov. 6. The presentation included data from in vitro functional studies, which showed that CA-170 can rescue effector functions of T cells (such as cytokine secretion) that are inhibited specifically by interactions of PD-L1/L2 and VISTA checkpoint proteins but does not impact T cells functions that are modulated as a result of interactions of other checkpoint regulators such as TIM-3, CTLA4, LAG-3 and BTLA with their respective counterparts. Additionally, studies conducted with isolated human T cells demonstrate that short exposures to CA-170 (in the order of a few hours) are adequate to rescue and sustain activation of T cells functions. Daily oral administration of CA-170 resulted in anti-tumor activity in multiple syngeneic tumor models including melanoma and colon cancer but no activity was observed in immune deficient SCID-Beige mice, suggesting that the anti-cancer effects of CA-170 are mediated via activation of immune responses to these cancers.

"The collective in vitro and animal model data are very compelling and strongly support testing of CA-170 in human clinical trials in multiple cancers," said Ali Fattaey, Ph.D., Curis’ President and CEO. "We are working with Aurigene to complete the IND enabling studies for CA-170 and initiate clinical studies in the first half of 2016."

IRAK4 inhibitor presentation:

Aurigene poster entitled "Efficacy of novel IRAK4 inhibitors in ABC-DLBCL and AML models" was presented on Sunday, Nov. 8. This presentation included data from chemically distinct series of small molecule compounds with potent IRAK4 inhibitory activity in biochemical assays. Anti-tumor activity of lead compounds was confirmed in a MYD88 mutant DLBCL xenograft tumor model. Lead compounds also inhibited inflammatory responses in an in vivo model, suggesting that IRAK4 inhibitors have the potential for use in the treatment of inflammatory diseases. Preliminary in vivo safety studies demonstrate a favorable therapeutic index for further development of lead compounds for potential human testing.