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Endocyte Presents Data at the 2017 CAR-TCR Summit Further Demonstrating the Ability to Manage Cytokine Release Syndrome Related to CAR T-Cell Therapy

On September 06, 2017 (GLOBE NEWSWIRE) — Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported in a poster session the presentation of new research from investigators at the company on the application of Endocyte’s SMDC technology in a chimeric antigen receptor (CAR) therapy setting (Poster #5 Targeting a universal CAR-T cell for effective anti-tumor activity and enhanced control using bi-specific small molecule adaptors) at the 2017 CAR-TCR Summit, in Boston, MA (Press release, Endocyte, SEP 6, 2017, View Source [SID1234520392]).

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"The clinical success and recent regulatory approval of the first CAR T-cell therapy has shown the efficacy of CAR T-cell technologies in hematological malignancies and the potential promise of the treatment in solid tumors as well. However, these therapies remain limited in their potential use due to hard to manage, clinically significant toxicities, specifically cytokine release syndrome (CRS). The data presented demonstrate the potential of Endocyte’s targeted bi-specific SMDC adaptors to improve upon the safety of current CAR T-cell approaches," said Mike Sherman, president and CEO at Endocyte. "This is particularly relevant as we advance our CAR-T program in solid tumors, including the previously announced clinical evaluation of our program in osteosarcoma being led by Dr. Michael Jensen of Seattle Children’s Research Institute."

Endocyte’s clinical plan includes genetically engineering a patient’s autologous T-Cells to express receptors that recognize fluorescein. Once these T-Cells are infused back into the patient, Endocyte researchers will then introduce its bi-specific adaptor molecules, which are constructed with both a fluorescein molecule and a tumor-homing molecule (e.g. folate) to precisely tether a universal CAR T-cell to a cancer cell. This approach causes local CAR T-cell activation within the tumor, followed by cancer cell death. The current presentation discloses an advancement of Endocyte’s method showing the application of specific blocking agents to control undesirable toxicity that often accompanies CAR-T therapy, including CRS, while simultaneously offering the potential to target multiple proteins on the diseased cell (folate, PSMA, NK1R, et al). Strategies are revealed for regulating cytokine storms, including: simple interruption or less frequent administration of the bi-specific adaptor, and injection of untethered folate or sodium fluorescein to rapidly (within hours) displace or block the bi-specific adaptor from bridging the cancer and CAR T-cells. Since the circulation half-life of most bi-specific adaptors is approximately 30 minutes, unwanted toxicity from CAR T-cell induced cytokine storms can be either pre-emptively prevented or rapidly suppressed following their emergence.

"Our pre-clinical data clearly show that a targeted bi-specific adaptor approach can effectively be used to more safely regulate CAR-T therapy for solid tumors," said Chris Leamon, Ph.D., vice president of research at Endocyte. "Knowing the unwanted toxicity can be controlled by administering clinically-approved agents is potentially a powerful advantage."

About Endocyte’s SMDC Bi-Specific Adaptors

Endocyte’s SMDC bi-specific adaptors represent a novel approach that makes possible the engineering of a single universal CAR T-cell, designed to bind with high affinity to FITC. This universal CAR T-cell can be specifically directed to cancer cells through the administration of a tumor targeted FITC-containing SMDC, known as a bi-specific adaptor that acts to bridge the universal CAR T-cell with the cancer cells to cause localized T-cell activation. This approach has been shown pre-clinically to address three key CAR T-cell issues by: (i) avoiding hyper-activation of CAR T-cells leading to a cytokine storm, (ii) enabling termination of CAR T-cell activity upon eradication of the tumor, and (iii) potentially enabling elimination of all cancer cells in heterogeneous solid tumors. In March 2017, Endocyte entered into a research collaboration with Seattle Children’s Research Institute and Dr. Michael Jensen for the development of Endocyte’s SMDC platform in CAR T-cell immunotherapy setting through the use of Endocyte’s proprietary SMDC bi-specific adaptor molecules.

Moleculin to Collaborate on Combining its WP1122 Brain Cancer Drug Candidate with Roche’s Drug Avastin

On September 6, 2017 Moleculin Biotech, Inc. (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it has entered into a collaborative agreement with the University of Bergen to test WP1122 in combination with the drug Avastin(R) (bevacizumab) made by Roche Pharma (Press release, Moleculin, SEP 6, 2017, View Source [SID1234520391]). Roche Pharma is not a party to the collaborative agreement.

"The potential for synergy with Roche’s drug is compelling," commented Walter Klemp, Chairman and CEO of Moleculin. "Avastin showed early promise in the treatment of brain tumors, but its usefulness has been hampered by the ability of brain tumors to develop resistance to anti-vascular therapy. Avastin prevents formation of new blood vessels including blood vessels that feed growing tumors and, as such, creates an environment where tumors become more dependent on glycolysis (a means of producing energy induced by a limited oxygen supply from the blood) enabling a potential form of therapy resistance. We’ve shown in animal models that WP1122 as an inhibitor of glycolysis limits tumor growth and increases survival in animals transplanted with human brain tumors, so it is logical to consider that WP1122 could potentially be an effective way to deal with Avastin resistance, as a follow up treatment, or in combination with Avastin."

"We have developed novel human brain tumor models in mice that display Avastin-resistance," added Dr. Rolf Bjerkvig, Professor at the Department of Biomedicine, University of Bergen in Norway, "that should allow us to validate the efficacy of WP1122 inhibition of Avastin-induced glycolysis. This may represent a breakthrough in treating brain tumors by using WP1122 in combination with Avastin. We are eager to explore this potential through our collaboration with Moleculin."

IGNYTA PROVIDES REGULATORY UPDATE ON ENTRECTINIB ROS1 LUNG CANCER DEVELOPMENT PROGRAM

On September 6, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that, based on recent FDA guidance, Ignyta has completed enrollment of the NDA registration efficacy data set of over 50 patients with ROS1 fusion-positive NSCLC for entrectinib, an orally bioavailable, CNS-active, tyrosine kinase inhibitor currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2 (Press release, Ignyta, SEP 6, 2017, View Source [SID1234520387]). In total, Ignyta has treated more than 70 ROS1 fusion-positive NSCLC patients with entrectinib across its ALKA, STARTRK-1, and STARTRK-2 studies. The U.S. Food and Drug Administration’s (FDA) most recent guidance confirmed that these studies will form the basis of a registrational dataset in ROS1 fusion-positive NSCLC; no additional studies were requested by FDA.

"We are grateful that FDA provided clear feedback on the regulatory path for Ignyta’s planned submission for entrectinib for the treatment of patients with ROS1 fusion-positive non-small cell lung cancer," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "With this feedback in hand, we remain on track to submit an NDA filing in the ROS1 NSCLC indication in the second half of 2018, to achieve 12 months of follow-up on all responders in the registrational data set."
The latest interaction with FDA has clarified the regulatory pathway for entrectinib in ROS1 NSCLC:

• Written feedback from the FDA confirmed that the NDA submission for ROS1-positive NSCLC will be based on three single arm studies, including two Phase 1 studies, ALKA and STARTRK-1, and the Phase 2 STARTRK-2 basket trial. No additional studies or confirmatory data were requested.

• Objective response rate (ORR), as assessed by blinded independent central review, was confirmed as the primary endpoint. FDA requested that all responding patients be followed for 12 months to assess durability of response.

• Entrectinib was intentionally designed to cross the blood-brain barrier and has demonstrated CNS activity. Specific guidance was provided by FDA on inclusion of entrectinib CNS efficacy data in future prescribing information.
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Interim data from STARTRK-2 on entrectinib in ROS1 lung cancer were shared in an investor update call in April 2017. An update on these data, including an additional six months of follow-up, will be presented at an upcoming medical conference in the fourth quarter of 2017.
"In our upcoming data presentation, we will further illuminate characteristics of entrectinib that may meaningfully differentiate the therapy in the eyes of prescribers, including duration of response, progression-free survival, CNS activity, and ongoing tolerability, which becomes more critical for patients as duration of response increases," said Pratik S. Multani, M.D., Chief Medical Officer of Ignyta. "We hope these updated data, along with centrally reviewed response rates, will further enhance the already compelling profile of entrectinib and its potential in ROS1 NSCLC."

Verastem Expands Duvelisib Development Program to Include Peripheral T-Cell Lymphoma

On September 6, 2017 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported the expansion of its duvelisib development program to include targeting the treatment of patients with Peripheral T-Cell Lymphoma (PTCL) (Press release, Verastem, SEP 6, 2017, View Source [SID1234520381]). Duvelisib has been granted Fast Track designation by the U.S. Food & Drug Administration (FDA) for the treatment of patients with PTCL who have received at least one prior therapy. Duvelisib, Verastem’s lead drug candidate, is an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma being investigated for the treatment of hematologic cancers, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), indolent non-Hodgkin lymphoma (iNHL) and other T cell lymphomas.

Development of duvelisib in PTCL is supported by compelling Phase 1 clinical data which demonstrated a 50% investigator-assessed overall response rate in 16 heavily pre-treated patients with relapsed or refractory PTCL, including 3 (19%) complete responses and 5 (31%) partial responses. Verastem intends to initiate an open-label, multicenter, Phase 2 clinical trial evaluating the efficacy and safety of duvelisib in patients with relapsed or refractory PTCL by year end 2017. Verastem expects that the Phase 2 study will be conducted in both the U.S. and Japan.
Today, the Company also announced the appointment of Brian Stuglik, RPh, to its Board of Directors. Mr. Stuglik brings to Verastem 35 years of experience in pharmaceutical and oncology commercialization in both the U.S. and international markets. He has successfully launched several multi-billion dollar brands over his career, including Gemzar, Alimta and Erbitux.

"Expansion of the duvelisib clinical development program, and the accompanying receipt of Fast Track designation from the FDA, are important steps in Verastem’s strategy to efficiently develop the potential of duvelisib in additional cancers such as T-cell malignancies," said Robert Forrester, President and Chief Executive Officer of Verastem. "PTCL is a rare and usually aggressive type of NHL where currently available therapies only provide modest benefit. We believe an oral monotherapy like duvelisib could be an important new treatment alternative for patients with T-cell Lymphomas, including PTCL, and we look forward to initiating a Phase 2 study in patients with relapsed or refractory disease by year end."

Mr. Forrester added, "Brian Stuglik is an accomplished executive with significant oncology commercialization expertise who can bring immediate value to Verastem as we now move towards commercializing duvelisib. He brings over 35 years of commercializing important novel oncology drugs together with his extensive external network of clinical thought leaders and deep industry connections. His experience will prove invaluable as we advance duvelisib toward the planned regulatory filing, and potential approval and commercialization."

Most recently, Mr. Stuglik has provided commercial and strategic consultancy services to a variety of life science companies as the founder of Proventus Health Solutions, LLC. Prior to Proventus, he served for over 30 years at Eli Lilly and Company, culminating in his role as Global Vice President and Chief Marketing Officer, Oncology Global Marketing, and advancing Lilly Oncology from a single brand and approved product to a portfolio of over 6 marketed or late-stage compounds across more than 10 cancer types. While at Lilly, Mr. Stuglik helped lead the efforts to acquire Imclone Systems and later led the integration and transition team for Lilly.

More About Fast Track Designation
The FDA defines Fast Track designation as a process designed to facilitate the development and expedite the review of drugs and biologics, to treat serious or life-threatening conditions, and to fill an unmet medical need. Specifically, Fast Track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support approval, and also provides the opportunity to submit sections of an NDA on a rolling basis as data become available.

About Peripheral T-Cell Lymphoma
Peripheral T-cell lymphoma (PTCL) is a rare, aggressive type of non-Hodgkin lymphoma (NHL) that develops in mature white blood cells called "T cells" and "natural killer (NK) cells"1 which circulate with the lymphatic system.2 PTCL accounts for between 10-15% of all non-Hodgkin lymphomas (NHLs) and generally affects people aged 60 years and older.1 Although there are many different subtypes of peripheral T-cell lymphoma, they often present in a similar way, with widespread, enlarged, painless lymph nodes in the neck, armpit or groin.2 There is currently no established standard of care for patients with relapsed or refractory disease.1

About the Tumor Microenvironment
The tumor microenvironment encompasses multiple tumor and non-tumor cell populations and an extracellular matrix that support cancer cell survival. This includes immunosuppressive regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, cancer-associated fibroblasts, and extracellular matrix proteins that can hamper the entry and therapeutic benefit of cytotoxic T-cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s product candidates, including duvelisib and defactinib, also target the tumor microenvironment to potentially improve response to therapy.

About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.3,4,5 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory CLL/SLL,6 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory iNHL.7 Both DUO and DYNAMO achieved their primary endpoints upon topline analysis of efficacy data. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T-cell lymphoma.8 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

Nordic Life Science Days in Malmö

On September 5, 2017 MonTa Biosciences reported that attends the Nordic Life Science Days in Malmö to meet with investors and pharma partners (Press release, MonTa Biosciences, SEP 5, 2017, View Source [SID1234618637]).