Rgenix To Present Abstract on RGX-019 at the 2019 AACR Annual Meeting

On April 1, 2019 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported that Isabel Kurth, Ph.D., Vice President of Research at Rgenix, will present an abstract about Rgenix’s RGX-019 program at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Rgenix, APR 1, 2019, View Source [SID1234534849]). The meeting is scheduled to take place Friday, March 29 through Wednesday, April 3 in Atlanta.

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 details of Rgenix’s presentation are as follows:


Event:
AACR Annual Meeting 2019

Date: April 3, 2019

Time: 8:00 A.M. – 12:00 P.M. EST

Description: Abstract LB-277/23, "Characterization of the anti-cancer and immunologic activity of RGX-019, a novel pre-clinical stage humanized monoclonal antibody targeting the MERTK receptor"

Location: Section 40, Georgia World Congress Center, 285 Andrew Young International Blvd
NW, Atlanta, GA 30313

Dr. Kurth will present data from pre-clinical research of RGX-019, a novel pre-clinical stage humanized monoclonal antibody targeting the MERTK receptor.

CELGENE RECEIVES THE CHMP’S POSITIVE OPINION FOR THE TRIPLETTE BASED ON REVLIMID ® (LENALIDOMIDE) AND IMNOVID ® (POMALIDOMIDE) IN COMBINATION WITH BORTEZOMIB AND DESAMETASONE IN MULTIPLE MYELOMA PATIENTS

On April 1, 2019 Celgene Corporation (NASDAQ: CELG) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has expressed a positive opinion for the two triplets in basis of the IMiD of Celgene, REVLIMID (lenalidomide) and IMNOVID (pomalidomide) (Press release, Celgene, APR 1, 2019, View Source [SID1234534848]).

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 CHMP recommended the approval of the extension of the lenalidomide indication as combination therapy with bortezomib and dexamethasone (RVd) for the treatment of adult patients with newly diagnosed multiple myeloma not eligible for transplantation.

The Committee also recommended the approval of pomalidomide in combination with bortezomib and dexamethasone (PVd) for the treatment of adult patients with multiple myeloma who have received at least one previous lenalidomide treatment.

The final decision of the European Commission, which generally conforms to the CHMP’s recommendations, is expected in about two months.

" The CHMP’s positive opinion regarding the RVd and PVd triplets represents an important extension of therapy options for patients with multiple myeloma, both newly diagnosed and relapsed / refractory after previous treatment lines, " commented Michele Cavo , Full Professor of Hematology, University of Bologna and Director of the "Seràgnoli" Hematology Institute, S. Orsola-Malpighi University Hospital, Bologna – In fact, RVd is configured as a more effective therapeutic alternative with respect to the current standards of first-line treatment of patients who are not eligible to receive an autologous transplant, to which it ensures a significant prolongation both of overall survival (whose median value was higher than 6 years in the pivotal study) that of disease-free progression survival (median value greater than 40 months). Instead, PVd represents one of the most effective combinations currently available for the rescue therapy of relapsed or refractory patients after previous exposure to lenalidomide, and in particular to those who have become refractory to it.» .

The CHMP’s positive opinion for lenalidomide was based on data from SWOG S0777, a phase 3 study that evaluated the triplet with lenalidomide, bortezomib and dexamethasone (RVd) in adult patients with previously untreated multiple myeloma, not immediately eligible for ASCT 1 . The results of the study showed statistically significant improvements both in terms of progression-free survival (PFS) and overall survival (OS) in patients treated with RVd compared to those treated with lenalidomide plus dexamethasone (Rd). The choice of first-line treatment is important 2since over time patients respond less and less to therapy, manifesting increasingly shorter periods of remission in subsequent treatment lines. 3

The CHMP’s positive opinion for PVd was based on data from OPTIMISMM, the first prospective phase 3 study that evaluated the use of the triplet with pomalidomide in patients previously treated with lenalidomide who in most cases (70%) were found refractory to it. 4 This patient population represents a growing unmet medical need for which new therapeutic options are needed.

The OPTIMISMM results showed a significantly higher progression-free survival in patients treated with PVd compared to patients in the Vd treatment arm.

" The positive opinions of the CHMP for our combinations of IMiD RVd and PVd represent wonderful news for patients with multiple myeloma living in Europe, " says Nadim Ahmed , President of the Hematology / Oncology Division of Celgene. " We now hope that the EMA will approve these therapeutic options by making them available to patients, as our goal is to improve their outcomes at different stages of the disease ."

Lenalidomide in combination with bortezomib and dexamethasone, as well as pomalidomide in combination with bortezomib and dexamethasone, are currently not approved in any country.

Information on Celgene immunomodulatory drugs

IMiD agents are small molecules available as an oral therapy for the treatment of certain hematological malignancies owned exclusively by Celgene. It is hypothesized that they have multiple mechanisms of action. It has been observed that T cell activation and proliferation, IL-2 protein proliferation and CD8 + effector T cell activity are observed to increase. They also influence the stimulation and expression of natural killer cells(NK) acting within the cellular environment with the aim of inducing the immune system to attack cancer cells and at the same time directly attack them. In addition to the immunomodulatory properties, a tumoricidal and antiangiogenic activity is also hypothesized. Celgene IMiDs represent a mainstay of research on multiple myeloma with a growing number of studies in combination therapies in different disease settings.

Information on multiple myeloma

Multiple myeloma is a potentially fatal haematological neoplasm, which is characterized by tumor proliferation and suppression of the immune system. 5.6 It is a rare but lethal disease: every year, in Europe, there are 42,000 diagnoses, with about 26,000 deaths due to the disease. 7 The typical course of multiple myeloma includes periods of symptomatic disease alternating with periods of remission and, with time, appearance of refractoriness (non-responsiveness). 8

Information on the SWOG study S0777

SWOG S0777 is a multicenter, phase 3, randomized open trial, aimed at evaluating the efficacy and safety of RVd compared to Rd in the treatment of patients with previously untreated multiple myeloma for whom an autologous transplant of stem cells (ASCT). 1

In this study, 525 patients with newly diagnosed multiple myeloma (NDM) were enrolled with symptomatic and measurable disease aged 18 years or older. Patients were randomized (1: 1) to receive initial lenalidomide treatment with bortezomib and dexamethasone (RVd group) or lenalidomide and dexamethasone therapy only (group Rd). Randomization was stratified based on the ISS stage ( International Staging System, I, II or III ) and intention to transplant (yes vs.no). The RVd regimen was administered in eight cycles lasting 21 days. Bortezomib was administered at a dose of 1.3 mg / m by IV route on days 1, 4, 8 and 11, in combination with oral lenalidomide 25 mg / day on days 1-14 plus oral dexamethasone at a dose of 20 mg / day on days 1, 2, 4, 5, 8, 9, 11 and 12. The Rd regimen was administered in six cycles lasting 28 days. The Rd standard regimen consisted of 25 mg / day of lenalidomide orally on days 1-21 plus 40 mg / day of dexamethasone orally on days 1, 8, 15 and 22. 1

The results of the SWOG S0777 1 study showed a significant improvement in median progression-free survival (mPFS) in patients treated with RVd vs. Rd (42 vs. 30 months; HR 0.76, 95% CI 0.62-0.94; P = 0.01). A significant improvement in median overall survival with respect to Rd was also observed with RVd (89 vs. 67 months; HR 0.72, 95% CI 0.56-0.94; P = 0.013). The overall response and complete response rates were superior in patients treated with RVd compared to Rd (global response: 82% RVd vs 72% Rd; complete response: 16% RVd vs. 8% Rd). The safety of RVd was also in line with the consolidated safety profiles of each drug in the triplet. 9.10

Upon completion of the induction, all patients received continuous maintenance therapy with lenalidomide orally at 25 mg once a day for 21 days plus oral dexamethasone at a dose of 40 mg once a day on days 1 , 8, 15 and 22 of each cycle lasting 28 days. 1

Information on the OPTIMISMM study

OPTIMISMM is the first phase 3 comparative study on the safety and efficacy of PVd vs. Vd, as an early therapy line in patients with relapsed and refractory multiple myeloma (with 1-3 previous therapeutic regimens) and previous exposure to lenalidomide, including patients refractory to it. 4

This international, multi-center, phase 3, randomized, open-label study involved 559 patients (281 patients in the PVd arm and 278 in the Vd arm) with previous demographic, basal and pathological features generally well balanced between the two treatment arms . The median number of previous treatment lines was two, while over one third of patients had received a previous treatment line (40% in both treatment arms). All patients had previously been treated with lenalidomide: most were refractory to lenalidomide (71% in the PVd vs. arm69% in the Vd arm); last treatment refractoriness was observed in 70% and 66% of cases respectively. The median follow-up was 16 months. 4

The results of the OPTIMISMM study showed a significantly higher PFS in patients treated with PVd compared to patients in the Vd arm (11.20 vs. 7.10 months [P = <0.0001, HR 0.61; 95% CI: (0.49-0.77)]), with a 39% reduction in the risk of disease progression or death in the PVd arm. In an exploratory analysis on the subgroup of patients undergoing a previous treatment line, the median progression-free survival (mPFS) was 20.73 months with PVd vs.11.63 months with Vd (HR 0.54; p = 0.0027). In these patients, the benefit of PVd was independent of refractoriness or non-refractory to previous lenalidomide therapy. The safety of PVd was in line with the established safety profiles of each drug in the triplet. 7.11

Patients were stratified according to the following criteria: age (≤75 years vs. > 75 years), number of previous therapeutic regimens for myeloma (1 vs. > 1) and β2-microglobulin levels (from <3.5 mg / L vs. ≥ 3.5 to ≤ 5.5 mg / L vs.> 5.5 mg / L). Patients were randomized 1: 1 to receive PVd or Vd. In 21-day cycles, patients received pomalidomide 4 mg / day on days 1-14 (PVd arm only); bortezomib 1.3 mg / m2 on days 1, 4, 8 and 11 of cycles 1-8 and on days 1 and 8 of cycle 9 and subsequent; and dexamethasone 20 mg / day (10 mg if age was> 75 years) on days when treatment with bortezomib was expected and on subsequent days. 4

Information on REVLIMID (lenalidomide)

Lenalidomide is approved in Europe as a monotherapy and is indicated for the maintenance therapy of adult patients with newly diagnosed multiple myeloma who have undergone an autologous stem cell transplant. Lenalidomide as a combination therapy is approved in Europe, the United States, Japan and about 25 other countries for the treatment of adult patients with multiple previously treated myeloma (MM) who are not eligible for transplantation. It is also approved in association with dexamethasone for the treatment of patients with MM who have received at least one previous therapy in almost 70 countries in Europe, the Americas, the Middle East and Asia

Lenalidomide is also approved in the United States, Canada, Switzerland, Australia, New Zealand and in several Latin American countries, as well as in Malaysia and Israel, for the treatment of transfusion-dependent anemia due to myelodysplastic syndromes (MDS) to low or intermediate-1 risk, associated with an isolated cytogenetic abnormality with deletion of 5q, with or without further cytogenetic abnormalities, as well as in Europe for the treatment of patients with transfusion-dependent anemia due to low or intermediate-1 myelodysplastic syndromes , associated with an isolated cytogenetic abnormality with deletion of 5q, in cases where other therapeutic options have proved insufficient or inadequate.

It is also approved in Europe and the United States for the treatment of patients with relapsed or refractory mantle lymphoma (MCL) after two previous therapies, one of which includes bortezomib. In Switzerland, Lenalidomide is indicated for the treatment of patients with relapsed or refractory MCL after previous therapy with bortezomib and chemotherapy / rituximab.

Lenalidomide is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical studies.

About IMNOVID (pomalidomide)

Pomalidomide administered in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have undergone at least two previous therapies, including both lenalidomide and bortezomib and with demonstrated progression of the disease during the last therapy. It belongs to the class of so-called immunomodulatory drugs (IMiD ).

Pomalidomide was initially approved in the United States in 2013 in association with dexamethasone for the treatment of patients with multiple myeloma who received at least two previous therapies including lenalidomide and a proteasome inhibitor and with demonstrated progression of the disease during or within 60 days of completion of the latest therapy.

In 2013 it was approved in the EU, in association with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma, who underwent at least two previous therapies, including both lenalidomide and bortezomib and with demonstrated progression of the disease during the last therapy.

It is also approved in a total of 66 countries in the world, including Australia, Canada, Japan and Switzerland, for use in association with dexamethasone for indications similar to those approved in the United States and the EU.

Genprex Provides Clinical, Corporate, and Financial Update for the Year Ending December 31, 2018

On April 1, 2019 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company developing a new approach to treating cancer based upon a novel proprietary technology platform, reported a clinical and corporate update and the filing of financial results for the year ended December 31, 2018 on Form 10-K with the United States Securities and Exchange Commission (Press release, Genprex, APR 1, 2019, View Source [SID1234534847]).

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!

"Over the past year, we made great progress in advancing the development of our gene therapy platform, including Oncoprex immunogene therapy for non-small cell lung cancer," said Rodney Varner, Chairman and Chief Executive Officer of Genprex. "I’m pleased with our progress and am excited to continue development of our gene therapies for cancer into 2019 and beyond. I’m confident, given all we’ve accomplished in the past year, that 2019 will be a landmark year for Genprex."

"As we continue to advance our clinical operations and manufacturing programs, Genprex is well positioned to make 2019 a pivotal year," Julien L. Pham, MD, MPH, President and Chief Operating Officer, stated. "From our successful IPO launch on NASDAQ, to completing a $10 million private placement, we are gaining momentum to reach the important milestones we set for ourselves."

Clinical Development and Corporate Update

Genprex’s accomplishments for 2018 and early 2019 include:

Completing its initial public offering and listing of common stock on NASDAQ Capital Market.
Completing a $10 million private placement.
Contracting with Accenture to provide clinical data management services to help accelerate the clinical development of Genprex’s lead drug candidate, Oncoprex.
Contracting with WIRB-Copernicus Group (WCG) to provide site selection and feasibility services, including Institutional Review Board (IRB) and Institutional Biosafety Committee (IBC) oversight for new clinical trial sites that Genprex anticipates adding to participate in its Phase I/II clinical trial evaluating the combination of Oncoprex and erlotinib (Tarceva) in non-small cell lung cancer (NSCLC).
Selecting 4Clinics as a CRO to provide clinical and regulatory support for Genprex’s clinical development program in the form of biostatistics, statistical programming and analysis, as well as medical and scientific writing for the Phase I/II clinical trial.
Entering into an agreement with the University of Texas at Austin Dell Medical School to establish executive offices at the school’s Health Discovery Building, joining the WorkSpaces @ Texas Health CoLab.
Establishing offices in Cambridge, MA, where Dr. Julien Pham, President and COO will oversee the clinical development of Genprex’s lead drug candidate, Oncoprex.
Entering into Amendment No. 2 to Clinical Trial Agreement with The University of Texas MD Anderson Cancer Center (MD Anderson) for continued conduct of Phase I/II clinical trial at MD Anderson.
Entering into a research agreement with MD Anderson for development of a therapeutic approach to treating cancer using TUSC2, the active agent in Genprex’s lead product candidate Oncoprex, in combination with immunotherapies; and for the development and the use of biomarkers to predict patient response to TUSC2 therapy.
Entering into an agreement with Aldevron, a leading contract manufacturing organization, to supply TUSC2 (Tumor Suppressor Candidate 2) plasmid DNA for use in Genprex’s clinical development program evaluating Oncoprex for the treatment of NSCLC.
Entering into agreements with additional contract manufacturing organizations to assist with manufacturing scale-up and transfer of manufacturing processes from manufacturing facilities of MD Anderson Cancer Center to commercial facilities.
Appointing Jan Stevens, RN as Vice President of Clinical Operations, Eric Chapdelaine as Senior Director of Pharmaceutical Sciences and Manufacturing, Kalyn Dabbs as Senior Manager of Communications and Marketing, and John N. Bonfiglio, Ph.D. to Board of Directors.
Launching a state-of-the-art website and overhauled corporate communications capabilities, including the introduction of a new investors email notification system.
2018 Financial Update

Genprex’s research and development expense was $971,427 for the year ended December 31, 2018, compared to $289,934 for the year ended December 31, 2017. This increase of $681,493 was due to the Company’s focus on improving clinical strategies, expanding research activities, refining existing manufacturing processes, and developing new manufacturing and logistics processes to support future research and development activities. Genprex had a cash position of $8.6 million as of December 31, 2018.

Turning Point Therapeutics’ Kinase Inhibitors Show High Potency against Targeted Oncogene Drivers and Their Mutations

On April 1, 2019 Turning Point Therapeutics, Inc., a clinical-stage precision oncology company designing and developing novel drugs to address treatment resistance, reported its data from four studies at AACR (Free AACR Whitepaper) 2019, highlighting potent activity of its kinase inhibitors, including repotrectinib against targeted oncogene drivers and many of their resistance mutations, and TPX-0022, a novel MET/CSF1R/SRC inhibitor (Press release, Turning Point Therapeutics, APR 1, 2019, View Source [SID1234534846]).

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!

Two studies highlighted the higher potency of repotrectinib as compared to other proxy investigational and the currently approved ROS1 and TRK tyrosine kinase inhibitors (TKIs), Xalkori and Vitrakvi, against fusion ROS1s, wildtype TRK, and many resistance mutations, including solvent front, gatekeeper, and compound mutations.

Alexander Drilon, M.D., Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and an investigator in the Phase 1 portion of the ongoing TRIDENT-1 study of repotrectinib, said, "As physicians adopt next-generation sequencing to identify genomic alterations in different cancers, there is an increased need for precision therapies that target specific oncogenes, such as TRK and ROS1. Repotrectinib was found to have 10-fold or higher increased potency when compared to proxy investigational and the currently approved TRK inhibitors against wildtype (WT) TRK fusions and solvent-front mutations. The findings — while early — are significant and warrant continued clinical study."

Data for TPX-0022, a novel, internally developed MET/CSF1R/SRC inhibitor approaching IND submission in 1H 2019, were presented for the first time at the conference. TPX-0022 was designed to target MET-driven tumor cells, but also modulate the tumor microenvironment by inhibition of CSF1R. This dual modulation has demonstrated significant tumor growth inhibition in preclinical models.

The data shown in two posters highlighted the ability of TPX-0022 to potently inhibit MET-driven cancer cells and the associated signaling of known cancer pathways, inhibiting tumor growth and reducing tumor associated macrophages. This dual mechanism of action showed tumor regression and growth inhibition in multiple xenograft tumor models harboring MET amplification or MET exon 14 skipping mutations.

"We are excited to share why we believe our lead asset, repotrectinib, is a potential best-in-class ROS1 and TRK targeted TKI," said Athena Countouriotis, M.D., chief executive officer. "This is based on multiple factors, including our ongoing Phase 1 TRIDENT-1 data and what we have shown at AACR (Free AACR Whitepaper) in terms of preclinical potency against fusion ROS1s and resistance mutations, as well as WT and resistance mutations within TRKA-C. We remain encouraged by the potential for repotrectinib to make a difference in the lives of patients with a range of oncogene drivers, both patients who have yet to be treated with a kinase inhibitor, as well as those who have been treated with a prior kinase inhibitor and developed treatment resistance through a specific mutation."

Turning Point Therapeutics plans to initiate a registrational Phase 2 portion of the TRIDENT-1 Study in the second half of 2019.

Dr. Countouriotis added: "While in late stage preclinical development, our MET/CSF1R/SRC kinase inhibitor, TPX-0022, has demonstrated promising preclinical activity in an important pathway for the regulation of tumor growth. We look forward to submitting our IND in the first half of 2019 and beginning our Phase 1 study in the second half of 2019."

Additional highlights from the four studies include:

Title: Repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations
Session: Sunday Mar 31, 2019, 1:00 PM – 5:00 PM
Abstract Number: 4000

Repotrectinib was shown to be more than 10-fold as potent as a LOXO-195 proxy against wildtype TRK fusions and solvent-front mutations, and more than 100-fold more potent against certain gatekeeper mutations. Repotrectinib was the only TRK inhibitor active against the compound mutation TRKA G595R/F589L (double mutation of solvent front and gatekeeper) in preclinical Ba/F3 cells. In xenograft tumor models, repotrectinib demonstrated significant tumor regression against wildtype or mutated TRK fusions. In the ongoing TRIDENT-1 clinical trial repotrectinib was active against the solvent front mutation ETV6-TRKC G623E in an entrectinib-resistant patient with a salivary gland tumor (-82%, confirmed partial response, RECIST v1.1). Tumor regression (-33%) was achieved in a larotrectinib-resistant cholangiocarcinoma patient with LMNA-TRKA G595R and F589L mutations.

Title: Repotrectinib, a new generation ROS1 inhibitor, is highly potent against fusion ROS1s and emerging resistance mutations
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 4832

Repotrectinib demonstrated higher potency as compared to other ROS1 inhibitors against multiple ROS1 fusions and mutations, especially the solvent front and gatekeeper mutations. In xenograft tumor models, repotrectinib treatment resulted in tumor regression against wildtype or solvent-front ROS1 fusion genes. Repotrectinib demonstrated a strong inhibition profile against wildtype and various mutated ROS1s across different fusion partners when compared to many other ROS1 TKIs.

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC for treatment of cancers with abnormal HGF/MET signaling
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3719

TPX-0022 potently inhibited cell proliferation of the MET-amplified MKN-45 (IC50 < 0.2 nM) and SNU-5 (IC50 < 0.2 nM) gastric cancer cells. TPX-0022 caused suppression of MET auto-phosphorylation at an IC50 of approximately 0.3 nM in MKN-45 cell line. TPX-0022 also potently inhibited the phosphorylation of MET downstream signaling effectors, including AKT, ERK, STAT3 and PLCγ2 in a dose-dependent manner. In the cancer cell line and patient-derived xenograft tumor models from gastric, lung and liver cancers harboring MET amplification or MET exon14 skipping mutations, TPX-0022 caused dramatic tumor regression and tumor growth inhibition. The tumor inhibitory effect was associated with drastic inhibition of MET activity.

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC inhibits tumor growth by promoting anti-tumor immune responses
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3749

TPX-0022 demonstrated potent CSF1R inhibitory activity and the ability to inhibit tumor growth and promote a pro-inflammatory anti-tumor microenvironment. In contrast, the potency of a proxy compound of the type II CSF1R inhibitor PLX-3397 demonstrated a strong dependency on the concentration of mouse CSF1, as the anti-proliferation IC50 shifted from <0.1 nM to 146.4 nM when CSF1 concentration changed from baseline to 1 ng/mL. Finally, in the MC38 syngeneic mouse model, TPX-0022 effectively reduced tumor associated macrophages (TAM), altered the polarity of TAMs toward a more M1 phenotype, increased cytotoxic T cells and inhibited the growth of MC38 tumors.

About Repotrectinib

Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small molecule kinase inhibitor of ROS1, TRKs and ALK. The clinical benefits of targeting ROS1, TRK, or ALK fusion kinases have been demonstrated with multiple kinase inhibitors already approved or in clinical studies. The successes of these therapies are often overshadowed by the development of acquired resistance. The acquired solvent front mutations including ROS1 G2032R, TRKA G595R and TRKC G623R, and ALK G1202R render common clinical resistance to the current ROS1, TRK, and ALK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ROS1, TRK and ALK kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple lines of treatment. Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ROS1, TRK or ALK in solid malignancies, and overcome multiple resistance mechanisms seen in resistant patients. Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements called TRIDENT-1 (www.clinicaltrial.gov number NCT03093116). Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [email protected].

Brian Tyler Becomes McKesson’s New CEO

On April 1, 2019 Veteran McKesson leader, reported that Brian Tyler, becomes the company’s new chief executive officer , succeeding John Hammergren. Hammergren has served as the company’s top executive since 1999 (Press release, McKesson, APR 1, 2019, View Source [SID1234534845]).

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!

"I am incredibly humbled and grateful for the opportunity to lead this company," said Brian Tyler, chief executive officer, McKesson Corporation. "We have a seasoned and talented Board of Directors and executives. I look forward to building on the solid foundation and global platform established by John and our management team. McKesson will continue to innovate in this changing healthcare environment, always focused on providing exceptional value to our customers and patients."

Tyler is a 22-year McKesson veteran who has headed up nearly every major business within the company as well as McKesson’s corporate strategy and business development unit. Most recently, Tyler served as COO and president of McKesson. He also joins the company’s Board of Directors.

Hammergren will remain Board chair for Change Healthcare and will continue to support Change Healthcare and McKesson as an advisor.

Edward Mueller becomes independent Board chair

Edward Mueller, previously lead independent director, takes over as independent chair of the company’s Board of Directors today and will provide strong leadership continuity for the Board. He has been a member of the company’s Board since April 2008 and the lead independent director since 2013.

Mueller served as chairman and chief executive officer of Qwest Communications from August 2007 to April 2011. He has also held the position of chief executive officer of Williams-Sonoma, Inc. and Ameritech Corporation, a subsidiary of SBC Communications. Mueller previously served on the boards for The Clorox Company, CenturyLink, Inc., Williams-Sonoma, Inc. and VeriSign, Inc.

Corporate headquarters relocates to Irving, Texas

Effective today, McKesson’s Las Colinas campus in Irving, Texas—just outside of Dallas—becomes the company’s official global corporate headquarters. Opened in 2017, the Las Colinas campus is an existing employee hub with teams performing vital functions for the company in areas such as operations, information technology, finance and accounting, marketing and sales, administration and support, purchasing, and project management.

"This is an exciting change for McKesson," said Brian Tyler. "Our Las Colinas campus offers us everything we could ask for—modern workspaces where our employees can connect and collaborate in a city with such great energy and growth. We look forward to deepening our connection in the community as a leading employer and corporate citizen. I know that we’ll thrive in the Dallas area."

The Las Colinas campus achieved LEED Gold certification, a recognition of its resource efficiency, and a WELL Building Silver certification, the first building standard focused solely on human health and wellness. Elements of the building are designed to support employee productivity and wellness, empowering employees to work the way they like while fostering team collaboration amidst an array of amenities and enhanced technology capabilities.

To learn more about career opportunities with McKesson at Las Colinas or other locations, visit the Careers page on the McKesson website.