On July 20, 2019 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported interim data from an ongoing investigator-sponsored clinical trial led by Baylor College of Medicine, evaluating the Company’s MultiTAA T cell therapy in patients with pancreatic adenocarcinoma (Clinical trial, Marker Therapeutics, JUL 20, 2019, View Source [SID1234537636]). The data were reviewed today in an oral presentation during a plenary session, as well as a poster presentation, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s (AACR) (Free AACR Whitepaper) Immune Cell Therapies for Cancer: Successes and Challenges of CAR T Cells and Other Forms of Adoptive Therapy conference held in San Francisco, California from July 19-22, 2019.

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"Pancreatic cancer continues to be one of the most challenging solid tumor malignancies to treat and survival rates have not seen a meaningful improvement in more than 40 years," said Brandon G. Smaglo, M.D., FACP, lead investigator and Assistant Professor of Oncology at Baylor College of Medicine. "We are encouraged by these interim data which suggest that MultiTAA therapy may contribute to more durable responses without added toxicity when used in combination with standard-of-care chemotherapy, or as a second-line therapy for patients who are chemo-refractory. Additionally, despite the particularly dense desmoplastic stroma surrounding pancreatic tumors—which has been long considered a major obstacle for T cell effectiveness—our study of patients with borderline surgically resectable disease suggests that MultiTAA cells are capable of meaningfully infiltrating the tumor."

Trial Overview

Title: Targeting pancreatic cancer using non-engineered, multi-antigen specific T cells (TACTOPS)

The trial plans to enroll a total of 45 patients with advanced or borderline resectable pancreatic adenocarcinoma in a three-arm trial. Arm A is for patients with unresectable/metastatic disease who are responding to standard first-line chemotherapy. Arm B is for patients with progressive disease or therapy intolerance. Arm C is an exploratory arm for patients with surgically resectable disease. To date, a total of 19 patients have been administered infusions of MultiTAA T cell therapy (ten patients in Arm A, six patients in Arm B and three patients in Arm C).

Interim Results

Arm A: This arm was designed to evaluate the safety and potential efficacy of using MultiTAA cells as part of first-line treatment for patients with pancreatic cancer. These patients in the chemo-responsive arm have completed or will complete at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) – the period during which a response to chemotherapy would typically occur – before receiving up to six administrations of MultiTAA T cells in conjunction with chemotherapy.

Out of the 9 evaluable patients (one patient was too early to be evaluated):
3 patients experienced objective responses after administration of MultiTAA cells
1 patient experienced a complete response
2 patients experienced partial responses
4 patients experienced stable disease; 2 patients within stable disease boundaries (+20%/-30%) saw reversal of tumor growth – tumors previously growing after chemotherapy alone showed shrinkage after administration of MultiTAA cells
1 patient experienced a mixed response (some lesions increased in size and others decreased for a net zero change in size of tumor lesions)
1 patient experienced disease progression
Overall tumor volume shrinkage was observed in six out of the eight patients with a measurable tumor after administration of MultiTAA cells. One evaluable patient did not have tumor measurements for analysis.
Of the 9 evaluable patients, over half have survived to or beyond the historical median overall survival associated with their respective chemotherapy regimens, and 7 of the 9 patients remain alive.
In patients responding to therapy, significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.
Arm B: This arm was designed to evaluate the use of MultiTAA cells as a second-line therapy for patients who have failed first-line chemotherapy. The patients in this chemo-refractory arm are either ineligible for chemotherapy or have progressed on chemotherapy and have received or are receiving up to six doses of MultiTAA T cells as a monotherapy.

Of the 6 patients treated and evaluable:
3 patients experienced stable disease or clinical disease stabilization
2 patients who previously had progressive disease experienced clinical disease stabilization for up to two months
1 has maintained stable disease for 7 months (ongoing)
3 experienced clinical decline
Among the patients who saw clinical disease stabilization, significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.
Arm C: This arm was designed to assess T cell infiltration and expansion. These patients with borderline surgically resectable disease received or will receive a dose of T cells following chemotherapy, radiotherapy or combination prior to surgical resection and up to five additional doses of T cells after surgery.

In these patients, MultiTAA T cells were measurable in meaningful numbers as detected by correlative analysis of resected tumor, and significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.
Overall, investigators observed a clinical benefit correlated with the detection of tumor-reactive T cells in patient peripheral blood (Arms A, B and C) and within tumor biopsy samples (Arm C) post-infusion. T cells exhibited activity against both targeted antigens as well as non-targeted TAAs including WT-1, AFP, MART-1 and numerous antigens of the MAGE family, indicating induction of antigen/epitope spreading.

No infusion-related systemic- or neurotoxicity was observed, and patients continue to be evaluated and enrolled in the trial.

Peter L. Hoang, President & CEO of Marker Therapeutics commented: "We are encouraged by the early clinical results we have seen in this clinical trial for patients who otherwise have few therapeutic options and a dire prognostic outcome, and we are optimistic about the prospect of potentially validating the use of MultiTAA therapy in the context of first-line and second-line care for patients with pancreatic adenocarcinoma. Moreover, we are very pleased with the data we see of MultiTAA T cell infiltration and subsequent epitope spreading observed in this trial, suggesting that MultiTAA therapy may initiate and contribute to a potent and durable treatment effect. We plan to continue following these patients and enroll new patients to further evaluate durability."

Conference Call and Webcast
For those unable to attend the presentations at AACR (Free AACR Whitepaper), Marker will host a conference call and webcast on Monday, July 22nd at 5:30am PDT/8:30am EDT featuring Dr. Brandon Smaglo, as well as Marker senior management. A live webcast of the investor presentation will be available in the investors section of the Company’s website at View Source and will be available for replay following the event.

About MultiTAA
Marker’s Multi-Antigen Targeted (MultiTAA) platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s blood capable of recognizing a broad range of tumor antigens. In early clinical trials, the multi-antigen approach has been well tolerated and shown to enhance tumor destroying capability and is one of the first therapies to consistently demonstrate epitope spreading – inducing the patient’s own T cells to expand, potentially contributing to a lasting anti-tumor effect. Unlike other cell therapies which require pre-conditioning regimens and hospitalization, MultiTAA is designed to be administered in an outpatient setting.

On July 19, 2019 Immatics Biotechnologies GmbH, a clinical-stage biopharmaceutical company active in the discovery and development of T-cell redirecting cancer immunotherapies, reported a comprehensive data set having completed the first cohort of the ACTolog Personalized Multi-Target T-cell Therapy Trial (Study code: IMA101-101, NCT02876510) at the AACR (Free AACR Whitepaper) Special Conference on Immune Cell Therapies for Cancer (Press release, Immatics Biotechnologies, JUL 19, 2019, http://investors.immatics.com/news-releases/news-release-details/immatics-presents-first-cohort-data-actologr-personalized-multi [SID1234569542]).

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ACTolog is an adoptive cell therapy (ACT) product using the patient’s own (autologous), non-genetically engineered (endogenous) T cells. "To our knowledge, this is the first time that patients are being treated with multiple defined cell therapy products directed against multiple specific tumor targets. For each of the T-cell products the actual expression of the targets is confirmed in a fresh tumor biopsy taken prior to product manufacturing. ACTolog is taking personalized cell therapy to the next level – aiming to provide effective treatments for patients with advanced solid cancers", states Dr. Harpreet Singh, CEO of Immatics.

The ACTolog approach has been pioneered by Prof. Cassian Yee at MD Anderson and expanded by Immatics to include multiple proprietary cancer targets discovered by Immatics’ XPRESIDENT platform. The trial is led by Principal Investigator Prof. Apostolia M. Tsimberidou and Co-Principal Investigator Prof. Borje S. Andersson with collaboration from other MD Anderson colleagues.

The data set will be provided in three oral presentations and two poster presentations by Prof. Tsimberidou, Dr. Nowak and Dr. Singh– for details see below.

The main conclusions from the currently available data set (N=9 patients, immune data for N=7 patients) are:

All patients entered the trial with progressive disease, having failed the previous line of therapy. Median duration of disease of the patients was 4 years (range 2-18 years) with a median of 6 previous rounds of treatment (range 3-12). Patients received a median of 2 target-specific ACTolog products (range 1-3).
ACTolog IMA101 is well tolerated. The most common adverse events, as expected, were cytopenias associated with the lymphodepleting regimen and Grade 1-2 cytokine release syndrome.
High frequencies and persistence of target-specific CD8+ T cells of up to 50% of peripheral CD8+ T cells (measured ex vivo) were observed within the blood of patients up to 12 weeks after adoptive transfer.
Comprehensive cellular immunomonitoring indicates a favorable phenotype of infused T cells.
All treated patients had stable disease by RECIST and irRECIST at 6 weeks and are alive to date after a median follow-up of 8 months.
The trial is part of a series of research programs and clinical trials conducted in a strategic alliance between Immatics and MD Anderson. The ACTolog T-cell products are manufactured at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in collaboration with The University of Texas Health Science Center in Houston (UTHealth).

On July 19, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that Janssen-Cilag International NV (Janssen) has submitted an extension application to the European Medicines Agency (EMA) for the subcutaneous delivery of DARZALEX (daratumumab) for patients with multiple myeloma (Press release, Halozyme, JUL 19, 2019, View Source [SID1234537628]).

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"We are pleased that Janssen’s filing follows quickly after its filing last week of a Biologics License Application (BLA) with the U.S. Food and Drug Administration," said Dr. Helen Torley, President and CEO. "We are particularly excited that, pending approval by the EMA, a greater number of patients with multiple myeloma may soon have a new therapeutic option that offers the potential of DARZALEX with a shorter administration time."

Janssen’s submission follows the announcement of positive results from its Phase 3 COLUMBA study, which investigated subcutaneously administered DARZALEX in comparison to intravenous DARZALEX in patients with relapsed and refractory multiple myeloma. Subcutaneous DARZALEX, using ENHANZE drug delivery technology, was found to be non-inferior to intravenous DARZALEX with regard to the co-primary endpoints of overall response rate and Maximum Ctrough concentration on day 1 of the third treatment cycle prior to dose.

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On July 19, 2019 Allergan plc (NYSE: AGN) reported that its Board of Directors has declared a cash dividend of $0.74 per ordinary share for the third quarter of 2019 (Press release, Allergan, JUL 19, 2019, View Source [SID1234537630]). The dividend will be paid on September 13, 2019 to shareholders of record at the close of business on August 13, 2019.

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On July 19, 2019, CASI Pharmaceuticals, Inc. ("CASI" or "Company"), reported that it has entered into an Open Market Sale AgreementSM (the "Sales Agreement") with Jefferies LLC ("Jefferies") (Filing, 8-K, CASI Pharmaceuticals, JUL 19, 2019, View Source [SID1234537631]). Pursuant to the terms of the Sales Agreement, the Company may elect to sell from time to time, at its option, up to $30 million shares of the Company’s common stock, par value $0.01 per share (the "Shares"), through Jefferies, as sales agent.

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Any sales of Shares pursuant to the Sales Agreement will be made under the Company’s effective "shelf" registration statement (the "Registration Statement") on Form S-3 (File No. 333-222046) which was declared effective on December 22, 2017 and the related prospectus supplement and the accompanying prospectus, as filed with the Securities and Exchange Commission (the "SEC") on July 19, 2019.

Under the terms of the Sales Agreement, the Company may elect to sell shares of its common stock through Jefferies by any method permitted that is deemed an "at the market offering" as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended (the "Securities Act"). Based upon the Company’s instructions (including any price, time or size limits or other customary parameters or conditions the Company may impose) Jefferies will use its commercially reasonable efforts consistent with its normal trading and sales practices to sell the Company’s common stock from time to time. Actual sales will depend on a variety of factors to be determined by the Company from time to time, including (among others) market conditions, the trading price of the Company’s common stock, capital needs and determinations by the Company of the appropriate sources of funding for the Company. The Company is not obligated to make any sales of common stock under the Sales Agreement and the Company cannot provide any assurances that it will issue any shares pursuant to the Sales Agreement. The Company will pay a commission rate of up to 3.0% of the gross sales price per share sold and agreed to reimburse Jefferies for certain specified expenses, including the fees and disbursements of its legal counsel in an amount not to exceed $90,000. The Company has also agreed pursuant to the Sales Agreement to provide Jefferies with customary indemnification and contribution rights.

The Company or Jefferies upon notice to the other, may suspend the offering of the Shares under the Sales Agreement at any time. The offering of the Shares pursuant to the Sales Agreement will terminate upon the sale of Shares in an aggregate offering amount equal to $30 million, or sooner if either the Company or Jefferies terminate the Sales Agreement pursuant to its terms.

The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The Sales Agreement is also incorporated by reference into the Registration Statement.

A copy of the opinion of Arnold & Porter Kaye Scholer LLP relating to the legality of the shares of Common Stock issuable under the Sales Agreement, is filed as Exhibit 5.1 to this Current Report on Form 8-K and is also incorporated by reference into the Registration Statement.

The above disclosure shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

The representations, warranties and covenants contained in the Sales Agreement were made solely for the benefit of the parties to the Sales Agreement. In addition, such representations, warranties and covenants (i) are intended as a way of allocating the risk between the parties to the Sales Agreement and not as statements of fact, and (ii) may apply standards of materiality in a way that is different from what may be viewed as material by stockholders of, or other investors in, the Company. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Sales Agreement, which subsequent information may or may not be fully reflected in public disclosures.