1stOncology™: Cancer Intelligence Service – Page 14408 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

ATARA BIOTHERAPEUTICS ANNOUNCES COLLABORATOR PRESENTATION OF POSITIVE PHASE 1 CLINICAL RESULTS FOR A MESOTHELIN-TARGETED CAR T IMMUNOTHERAPY IN PATIENTS WITH ADVANCED MESOTHELIOMA

On March 31, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborators at Memorial Sloan Kettering Cancer Center (MSK), Prasad S. Adusumilli, M.D., and Michel Sadelain, M.D., Ph.D., presented encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following prior standard platinum-containing chemotherapy (Press release, Atara Biotherapeutics, MAR 31, 2019, View Source [SID1234534786]). Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed encouraging anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The findings will be presented today in the Advances in Novel Immunotherapeutics oral session at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia.

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!

"Clinical results presented by our MSK collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establish an important proof-of-concept advance for CAR T immunotherapy in solid tumors," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "These encouraging safety results and anti-tumor responses observed by lead investigator Dr. Adusumilli in combination with a PD-1 checkpoint inhibitor, support our plans to progress development of a next-generation, mesothelin-targeted CAR T immunotherapy using MSK’s novel 1XX CAR signaling domain and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies for patients with mesothelin-associated solid tumors."

The Phase 1 clinical study recruited 21 patients, 19 with malignant pleural mesothelioma (MPM), one with metastatic lung cancer and one with metastatic breast cancer, who received a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study included six dose cohorts with administration directly to the tumor site using regional delivery techniques, initially at a low CAR T dose without lymphodepleting chemotherapy, followed by increasing CAR T dose cohorts with lymphodepletion. A subset of these patients was subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor.

Mesothelin-targeted, autologous CAR T administration was found to be generally well-tolerated with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters. CAR T cells were found to be persistent in the peripheral blood for 13 of the 21 patients during the 38-week evaluation, and their presence was associated with evidence of tumor regression on imaging studies.

Best overall response rate (ORR) for a subset of 11 MPM patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses (CMR) on PET imaging and 6 partial responses (PR). Six of the 11 patients in this subset were programmed cell death ligand 1 (PD-L1) negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 4 of the 8 total responses observed in PD-L1 negative patients (1 CMR and 3 PR).

Following progression on standard platinum-containing chemotherapy, the expected ORR for patients with MPM treated with a checkpoint inhibitor is estimated between 5%-29% with one patient achieving a CR across multiple studies.1-5

MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer (NCT02792114). Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

Presentation CT036: A Phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy
Session CTMS01: Advances in Novel Immunotherapeutics
Presentation Date and Time:Sunday, March 31, 2019 from 3:20 pm – 3:35 pm EDT
Location:Room A411 – Georgia World Congress Center
Authors:Prasad S. Adusumilli, Marjorie Zauderer, Valerie Rusch, Roisin O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Alain Vincent, Elizabeth Halton, Claudia Diamonte, John Pineda, Shanu Modi, Steve Solomon, David R Jones, Renier Brentjens, Isabelle Riviere, Michel Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center

Maverick Therapeutics to Unveil Pre-Clinical Data on Novel COBRATM Platform at American Association for Cancer Research 2019 Annual Meeting

On March 30, 2019 Maverick Therapeutics Inc., a private biopharmaceutical company pioneering next-generation redirected T-cell targeted immunotherapies, reported that it will unveil pre-clinical data characterizing its novel COBRATM therapeutic platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held from March 29 to April 3 in Atlanta, Georgia (Press release, Maverick Therapeutics, MAR 30, 2019, View Source [SID1234534787]). COBRA is the most advanced bispecific T-cell engaging platform in its class, designed to safely target solid tumors with highly specific and potent activity. These pre-clinical data characterize the conditional and potent activity of the COBRATM platform in vitro as well as demonstrate the regression of established solid tumors in in vivo models.

COBRATM is a proprietary approach to cancer immunotherapy. The COBRATM molecules are designed to bind to a specific target but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. Focusing T-cell activation and killing at the tumor site is ideal for the treatment of solid tumors, which account for 90% of all cancers1. COBRATM molecules include a component that extends their half-life in the circulation prior to activation within the tumor site; once activated, this component is lost, allowing the active molecules to then be cleared from the body more rapidly after targeting and killing the cancer cells. This further increases their safety window by reducing the potential for active COBRATM molecules to travel outside the tumor to healthy tissues and cause damage.

"We are encouraged by the inaugural data on our proprietary COBRATM platform, as they provide proof-of-concept for our approach to overcome the challenges current T-cell engagers face when addressing solid tumors," said Maverick Therapeutics Chief Executive Officer Jim Scibetta. "With its scientifically elegant design, COBRATM has the potential to deliver increased specificity, higher potency and reduced toxicity, all of which may help extend both the duration and quality of life of people living with solid tumor cancers."

Full abstracts are available online at View Source Details of the poster presentation are listed below.

Title: COBRATM: A Novel Conditionally Active Bispecific Antibody that Regresses Established Solid Tumors in Mice
Session Title: Immunology – Therapeutic Antibodies 1
Abstract Number: 557
Poster Board Number: 21
Presentation Time: Sunday, March 31, 1pm – 5pm ET
Location: Georgia World Congress Center – Exhibit Hall B, Poster Section 23

About COBRA Therapeutic Platform

The company’s proprietary COBRA, or COnditional Bispecific Redirected Activation, therapeutic platform is the most advanced bispecific T-cell engagement platform, designed to target solid tumors with highly potent and specific activity, while avoiding damage to normal healthy tissues. COBRATM molecules are designed to bind to a specific target, but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. COBRATM molecules include a component that extends their presence in the circulation prior to activation within the tumor site; once activated this component is lost, allowing the active molecule to then be cleared from the body more rapidly after targeting and killing the cancer cells. This increases their safety window by reducing the potential for active COBRA molecules to escape the tumor and travel to healthy tissues.

Immunomic Therapeutics Presents Late-Breaking Preclinical Data on DNA Vaccine ITI-7000 at AACR 2019

On March 29, 2019 Immunomic Therapeutics, Inc. reported its late-breaking preclinical data which shows that its investigational nucleic acid platform, UNITE, may enhance antitumor immunity when used in connection with its investigational DNA vaccine, ITI-7000 (Press release, Immunomic Therapeutics, MAR 29, 2019, View Source [SID1234534890]). In preclinical studies, ITI-7000, an investigational DNA vaccine targeting ErbB2/HER2, demonstrated robust activation of known anti-tumor CD4 and CD8 cells in vivo and promoted tumor infiltration with activated CD8 T cells. These data are presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 meeting in Atlanta, Georgia.

In addition to observing activation of known anti-tumor CD4 and CD8 cells in vivo, Immunomic scientists observed the overexpression of PDL1 in the tumor microenvironment. This pathway has shown clinical relevance as a cancer immunotherapy target of the tumor microenvironment. PDL1 overexpression upregulated by ITI-7000 suggests that a combination of ITI-7000 with an anti-PD1/PDL1 therapy may increase the therapeutic potential of either agent on its own. This data also supports the prevailing belief in the immunotherapy community that cancer vaccination could synergize with anti PD1 and PDL1 and other immunotherapies, as well as support the viability of the UNITE platform as a means to do so. In summary, these findings support the potential of ITI-7000 as a cancer vaccine and highlight that UNITE, Immunomic’s nucleic acid platform, may have the potential to enhance immunity of investigational cancer therapies.

View the poster.

Poster Title: DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells
Session Category: Immunology
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 2, 2019 8:00 AM- 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 42

Aileron Therapeutics Announces Pricing of $26M Private Placement

On March 29, 2019 Aileron Therapeutics (NASDAQ: ALRN), the clinical-stage leader in the field of stabilized cell-permeating peptides to treat cancer and other diseases, reported that it has entered into a securities purchase agreement with a group of institutional accredited investors for the private placement of $26 million of Aileron common stock and warrants (Press release, Aileron Therapeutics, MAR 29, 2019, View Source [SID1234534815]). The private placement is expected to close on or about April 2, 2019 subject to the satisfaction of customary closing conditions.

The private placement was led by Satter Medical Technology Partners, L.P. with significant additional participation from Jennison Associates (on behalf of certain clients) and an undisclosed institutional investor, in addition to other new and existing investors.

The Company is selling in the private placement 11,838,582 units, consisting of 11,838,582 shares of common stock and associated warrants to purchase 11,838,582 shares of common stock, for a combined price of $2.01 per unit. In addition, the Company is also selling in the private placement 1,096,741 units, consisting of pre-funded warrants to purchase 1,096,741 shares of common stock and associated warrants to purchase 1,096,741 shares of common stock, for a combined price of $2.01 per unit.

William Blair & Company, L.L.C. will act as sole placement agent in connection with the financing.

Aileron expects to receive aggregate gross proceeds of approximately $26 million, before deducting placement agent fees and offering expenses, and excluding the exercise of any warrants. Aileron expects to use the net proceeds from the financing to fund the further advancement of its ALRN-6924 clinical trials and research programs, including its ongoing clinical trial collaboration with Pfizer testing ALRN-6924 in combination with palbociclib in MDM2-amplified cancers and its planned Phase 1b/2 clinical trial to evaluate ALRN-6924 as a myelopreservative agent, to protect against chemotherapy-induced toxicity. This use of proceeds reflects Aileron’s determination to cease enrollment and clinical development in AML/MDS in light of the Company’s resources and its assessment of the commercial opportunities, as well as the changed competitive landscape where seven drugs were approved for AML in the United States in the last two years.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or applicable state securities laws, and accordingly may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. Aileron has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of

common stock issued in the private placement and the shares of common stock issuable upon the exercise of the warrants issued in the private placement.

This release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be by means of a prospectus.

Autolus Therapeutics Announces Conference Call to Discuss AUTO1 ALLCAR19 Data Presentation at the AACR Annual Meeting 2019

On March 29, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, reported that management will host a conference call and webcast on Tuesday, April 2, 2019 at 8:00 am ET / 1:00 pm BST to discuss initial data on the AUTO1 ALLCAR19 Phase 1/2 trial in adult acute lymphoblastic leukemia (ALL) being presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 1, 2019 in Atlanta, Georgia (Press release, Autolus, MAR 29, 2019, View Source [SID1234534795]).

Claire Roddie, MB PhD FRCPath, consultant hematologist, University College London Hospital and honorary senior lecturer, University College London, will deliver the poster presentation. Details include:

Abstract Number: CT105
Session Name: PO.CT04 – Phase I-III Trials in Progress: Part 1
TITLE: AUTO 1, a novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL
Session Date: Monday, April 1, 2019
Session Time: 1:00 PM – 5:00 PM ET
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 17

The full text of the abstract is available on the AACR (Free AACR Whitepaper) website at View Source!/6812/presentation/9977.

Conference Call Information
Autolus management will host a conference call featuring Dr. Roddie on Tuesday, April 2, 2019 at 8:00 am ET/ 1:00 pm BST to discuss the ALLCAR19 data presented at AACR (Free AACR Whitepaper). To listen to the webcast and view the accompanying slide presentation, please go to View Source

The call may also be accessed by dialing 866-679-5407 (U.S.) or 409-217-8320 (international) and referencing conference ID 7679666. After the conference call, a replay will be available for one week. To access the replay, please dial 855-859-2056 (U.S.) or 404-537-3406 (international) and enter conference ID 7679666.

About AUTO1
AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety – while maintaining similar levels of efficacy – compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells’ abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 trials, one in pediatric ALL and one in adult ALL.
For information about the trials, visit View Source and
View Source

About Adult Acute Lymphoblastic Leukemia
According to the American Cancer Society, acute lymphoblastic leukemia (ALL) is predicted to affect approximately 5,960 adults in the United States in 2018. Combination chemotherapy enables 90% of adult patients to experience CR (complete response). Despite this, the prognosis of adult ALL is still poor and has not changed significantly during the last two to three decades, with long-term remission rates limited to 30–40%. Approximately 50% of all adult ALL patients will relapse.